Chromosomal organization and evolutionary conservation of the human chromosome 19q linkage group containing three DNA repair genes

A series of human-rodent somatic cell hybrids were investigated by Southern blot analysis for the presence or absence of twenty-six molecular markers and three isozyme loci from human chromosome 19. Based on the co-retention of these markers in the various independent hybrid clones containing portions of human chromosome 19 and on pulsed field mapping, chromosome 19 is divided into twenty ordered regions. The most likely marker order for the chromosome is: (LDLR, C3)-(cen-MANNB)-D19S7-PEPD-D19S9-GPI-TGF$ \beta$-(CYP2A, NCA, CGM2, BCKAD)-PSG1a-(D19S8, XRCC1)-(D19S19, ATP1A3)-(D19S37, APOC2)-CKMM-ERCC2-ERCC1-(D19S62, D19S51)-D19S6-D19S50-D19S22-(CGB, FTL)-qter.^ The region of 19q between the proximal marker D19S7 and the distal gene coding for the beta subunit of chorionic gonadotropin (CGB) is about 37 Mb in size and covers about 37 cM genetic distance. The ration of genetic to physical distance on 19q is therefore very close to the genomic average OF 1 cM/Mb. Estimates of physical distances for intervals between chromosome 19 markers were calculated using a mapping function which estimates distances based on the number of breaks in hybrid clone panels. The consensus genetic distances between individual markers (established at HBM10) were compared to these estimates of physical distances. The close agreement between the two estimates suggested that spontaneously broken hybrids are as appropriate for this type of study as radiation hybrids.^ All three DNA repair genes located on chromosome 19 were found to have homologues on Chinese hamster chromosome 9, which is hemizygous in CHO cells, providing an explanation for the apparent ease with which mutations at these loci were identified in CHO cells. Homologues of CKMM and TGF$\beta$ (from human chromosome 19q) and a mini-satellite DNA specific to the distal region of human chromosome 19q were also mapped to Chinese hamster 9. Markers from 19p did not map to this hamster chromosome. Thus the q-arm of chromosome 19, at least between the genes PEPD and ERCC1, appears to be a linkage group which is conserved intact between humans and Chinese hamsters. ^

Regression of the inflammatory microenvironment of the peritoneal cavity in women with endometriosis by GnRHa treatment.

OBJECTIVE To investigate the effect of gonadotropin-releasing hormone analogues (GnRHa) on the peritoneal fluid microenvironment in women with endometriosis. STUDY DESIGN Peritoneal fluid was collected from 85 women with severe endometriosis (rAFS stage III and IV) during laparoscopic surgery during the proliferative phase. Prior to surgery clinical data were collected. The concentrations of specific markers for endometriosis in the peritoneal fluid were determined using an ELISA and a comparison between peritoneal fluid markers in women using GnRHa and no hormonal treatment was performed using a non-parametric Mann-Whitney U test. RESULTS The study included peritoneal fluid from 39 patients who had been administered GnRHa (Zoladex(®)) in the three months prior to surgery and 46 from women with no hormonal treatment in this period. Concentrations of IL-8, PAPP-A, glycodelin-A and midkine were significantly reduced in the GnRHa treatment group compared to women receiving no hormonal treatment. RANTES, MCP-1, ENA-78, TNF-α, OPG, IP-10 and defensin showed no significant change between the two groups. CONCLUSIONS GnRHa mediate a significant regression in the inflammatory nature of the peritoneal microenvironment in women with endometriosis.

Exogenous gonadotropins do not increase the blood-follicular transportation capacity of extra-ovarian hormones such as prolactin and cortisol.

BACKGROUNDS In vitro fertilization involves high dosage gonadotropin stimulation, which apparently has some negative impact on follicular endocrine function. As chorionic gonadotropin stimulation has been shown to increase the blood-follicular permeability in animal models, this raises the question if such an effect also applies to gonadotropins in humans, possibly affecting the endocrine follicular milieu. FINDINGS Follicular fluid and serum were collected at the time of follicular aspiration in in vitro fertilisation without (Natural cycle IVF, n = 24) and with (conventional gonadotropin stimulated IVF, n = 31) gonadotropin stimulation. The concentration of the extra-ovarian hormones prolactin and cortisol were analysed by immunoassays. RESULTS Median serum prolactin and cortisol concentrations were 12.3 ng/mL and 399 nmol/L without versus 32.2 ng/mL and 623 nmol/L with gonadotropin stimulation. The corresponding concentrations in follicular fluid were 20.6 ng/mL and 445 nmol/L versus 28.8 ng/ml and 456 nmol/L for prolactin and cortisol. As a consequence, mean follicular fluid:serum ratios were significantly reduced under gonadotropin stimulation (prolactin p = 0.0138, cortisol p = 0.0001). As an enhanced blood-follicular permeability and transportation, induced by gonadotropin stimulation, would result in increased instead of decreased follicular fluid:serum ratios as found in this study, it can be assumed that this does not affect extra-ovarian protein and steroid hormones as illustrated by prolactin and cortisol. CONCLUSIONS The model of serum follicular fluid:serum ratio of hormones, produced outside the ovaries, did not reveal a gonadotropin induced increased blood-follicular transportation capacity. Therefore it can be assumed that the effect of gonadotropins on follicular endocrine function is not due to an increased ovarian permeability of extra-ovarian hormones.

Ovarian and uterine development and hormonal feedback mechanism in a 46 XX patient with CYP19A1 deficiency under low dose estrogen replacement.

Abstract Background: Aromatase deficiency may result in a complete block of estrogen synthesis because of the failure to convert androgens to estrogens. In females, this results in virilisation at birth, ovarian cysts in prepuberty and lack of pubertal development but virilisation, thereafter. Objective and methods: We studied the impact of oral 17β-estradiol treatment on ovarian and uterine development, and on LH/FSH and inhibin B during the long-term follow-up of a girl harboring compound heterozygote point mutations in the CYP19A1 gene. Results: In early childhood, low doses of oral 17β-estradiol were needed. During prepuberty treatment with slowly increasing doses of E2 resulted in normal uterine and almost normal development of ovarian volume, as well as number and size of follicles. Regarding hormonal feedback mechanisms, inhibin B levels were in the upper normal range during childhood and puberty. Low doses of estradiol did not suffice to achieve physiological gonadotropin levels in late prepuberty and puberty. However, when estradiol doses were further increased in late puberty levels of both FSH and LH declined with estradiol levels within normal range. Conclusion: Complete aromatase deficiency provides an excellent model of how ovarian and uterine development in relation to E2, LH, FSH and inhibin B feedback progresses from infancy to adolescence.

Modified natural cycle in vitro fertilization an alternative in vitro fertilization treatment with lower costs per achieved pregnancy but longer treatment time

OBJECTIVE To analyze the cost and time requirement per achieved pregnancy in optimized modified natural cycle in vitro fertilization (mNC-IVF) based on a treatment protocol with very few consultations and to compare those with conventional gonadotropin-stimulated aVF (clVF) cycles. STUDY DESIGN Mono centric prospective trial. Eighty infertile patients each received 1 modified mNC-IVF cycle using low doses of the clomiphene citrate. Based on the number of consultations and the clinical pregnancy rate per cycle, the total costs and required time to achieve a pregnancy were analyzed and compared with cIVF. Calculations for cIVF were based on standard therapy protocols and outcomes of European registries. RESULTS Patients (21-42 years old, 35.4 +/- 4.7 years) undergoing mNC-IVF required on average 1.2 consultations before follicle aspiration. Pregnancy rate per transfer and per initiated cycle were 25% and 13.6%, respectively. Multiple pregnancies did not occur. According to the calculations, total costs per pregnancy rate were around 15% lower with mNC-IVF as compared to cIVF. In contrast, time to achieve an equal pregnancy rate was calculated to take around 30% longer with mNC-IVF as compared to cIVF. CONCLUSION mNC-IVF using very low dosages of clomiphene citrate avoids multiple pregnancies and is less expensive but more time consuming per achieved pregnancy when compared to clVF.

Serum but not follicular fluid cytokine levels are increased in stimulated versus natural cycle IVF: a multiplexed assay study.

Throughout follicular growth the number of immune cells increases, enhanced under stimulation with exogenous gonadotropins. This treatment, however, may adversely influence folliculogenesis and negatively affect oocyte quality through modifications in the follicular concentrations of cytokines released by these immune cells. We studied this hypothesis by systematically analysing the concentrations of cytokines present in the serum and follicular fluid at the time of follicular aspiration in conventional gonadotropin-stimulated (c-IVF) cycles in comparison with natural cycle IVF (NC-IVF) in which the follicles were naturally matured. Our study involved 37 NC-IVF and 39 c-IVF cycles including 13 women who underwent both therapies. Mean age was 35.3 ± 4.6 (SD) and 34.2 ± 3.7 years in the NC-IVF and c-IVF groups (ns). Thirteen cytokines were determined in matched serum and FF samples. Interleukin (IL)-4, TNF-α, RANTES, eotaxin and interferon-gamma-induced protein-10 concentrations were lower in FF than in serum. IL-6, -8, -10, -18, monocyte chemotactic protein-1 (MCP-1), VEGF and leukaemia inhibitory factor (LIF) showed higher median levels in FF than in serum, indicating possible ovarian production. Most of these markers were also increased in concentration in the stimulated (c-IVF) than in the NC groups in the serum, but not in the follicular fluid. This finding can be attributed to the increased number of active follicles present after controlled ovarian stimulation. IL-8 was reduced in c-IVF cycles. Our study did not reveal differences in follicular fluid but in serum cytokine concentrations, suggesting that the follicular immune system might not be significantly affected by gonadotropin stimulation.

Adjuvant exemestane with ovarian suppression in premenopausal breast cancer.

BACKGROUND Adjuvant therapy with an aromatase inhibitor improves outcomes, as compared with tamoxifen, in postmenopausal women with hormone-receptor-positive breast cancer. METHODS In two phase 3 trials, we randomly assigned premenopausal women with hormone-receptor-positive early breast cancer to the aromatase inhibitor exemestane plus ovarian suppression or tamoxifen plus ovarian suppression for a period of 5 years. Suppression of ovarian estrogen production was achieved with the use of the gonadotropin-releasing-hormone agonist triptorelin, oophorectomy, or ovarian irradiation. The primary analysis combined data from 4690 patients in the two trials. RESULTS After a median follow-up of 68 months, disease-free survival at 5 years was 91.1% in the exemestane-ovarian suppression group and 87.3% in the tamoxifen-ovarian suppression group (hazard ratio for disease recurrence, second invasive cancer, or death, 0.72; 95% confidence interval [CI], 0.60 to 0.85; P<0.001). The rate of freedom from breast cancer at 5 years was 92.8% in the exemestane-ovarian suppression group, as compared with 88.8% in the tamoxifen-ovarian suppression group (hazard ratio for recurrence, 0.66; 95% CI, 0.55 to 0.80; P<0.001). With 194 deaths (4.1% of the patients), overall survival did not differ significantly between the two groups (hazard ratio for death in the exemestane-ovarian suppression group, 1.14; 95% CI, 0.86 to 1.51; P=0.37). Selected adverse events of grade 3 or 4 were reported for 30.6% of the patients in the exemestane-ovarian suppression group and 29.4% of those in the tamoxifen-ovarian suppression group, with profiles similar to those for postmenopausal women. CONCLUSIONS In premenopausal women with hormone-receptor-positive early breast cancer, adjuvant treatment with exemestane plus ovarian suppression, as compared with tamoxifen plus ovarian suppression, significantly reduced recurrence. (Funded by Pfizer and others; TEXT and SOFT ClinicalTrials.gov numbers, NCT00066703 and NCT00066690, respectively.).

Interventions for hirsutism (excluding laser and photoepilation therapy alone)

BACKGROUND Hirsutism occurs in 5% to 10% of women of reproductive age when there is excessive terminal hair growth in androgen-sensitive areas (male pattern). It is a distressing disorder with a major impact on quality of life. The most common cause is polycystic ovary syndrome. There are many treatment options, but it is not clear which are most effective. OBJECTIVES To assess the effects of interventions (except laser and light-based therapies alone) for hirsutism. SEARCH METHODS We searched the Cochrane Skin Group Specialised Register, CENTRAL (2014, Issue 6), MEDLINE (from 1946), EMBASE (from 1974), and five trials registers, and checked reference lists of included studies for additional trials. The last search was in June 2014. SELECTION CRITERIA Randomised controlled trials (RCTs) in hirsute women with polycystic ovary syndrome, idiopathic hirsutism, or idiopathic hyperandrogenism. DATA COLLECTION AND ANALYSIS Two independent authors carried out study selection, data extraction, 'Risk of bias' assessment, and analyses. MAIN RESULTS We included 157 studies (sample size 30 to 80) comprising 10,550 women (mean age 25 years). The majority of studies (123/157) were 'high', 30 'unclear', and four 'low' risk of bias. Lack of blinding was the most frequent source of bias. Treatment duration was six to 12 months. Forty-eight studies provided no usable or retrievable data, i.e. lack of separate data for hirsute women, conference proceedings, and losses to follow-up above 40%.Primary outcomes, 'participant-reported improvement of hirsutism' and 'change in health-related quality of life', were addressed in few studies, and adverse events in only half. In most comparisons there was insufficient evidence to determine if the number of reported adverse events differed. These included known adverse events: gastrointestinal discomfort, breast tenderness, reduced libido, dry skin (flutamide and finasteride); irregular bleeding (spironolactone); nausea, diarrhoea, bloating (metformin); hot flushes, decreased libido, vaginal dryness, headaches (gonadotropin-releasing hormone (GnRH) analogues)).Clinician's evaluation of hirsutism and change in androgen levels were addressed in most comparisons, change in body mass index (BMI) and improvement of other clinical signs of hyperandrogenism in one-third of studies.The quality of evidence was moderate to very low for most outcomes.There was low quality evidence for the effect of two oral contraceptive pills (OCPs) (ethinyl estradiol + cyproterone acetate versus ethinyl estradiol + desogestrel) on change from baseline of Ferriman-Gallwey scores. The mean difference (MD) was -1.84 (95% confidence interval (CI) -3.86 to 0.18).There was very low quality evidence that flutamide 250 mg, twice daily, reduced Ferriman-Gallwey scores more effectively than placebo (MD -7.60, 95% CI -10.53 to -4.67 and MD -7.20, 95% CI -10.15 to -4.25). Participants' evaluations in one study with 20 participants confirmed these results (risk ratio (RR) 17.00, 95% CI 1.11 to 259.87).Spironolactone 100 mg daily was more effective than placebo in reducing Ferriman-Gallwey scores (MD -7.69, 95% CI -10.12 to -5.26) (low quality evidence). It showed similar effectiveness to flutamide in two studies (MD -1.90, 95% CI -5.01 to 1.21 and MD 0.49, 95% CI -1.99 to 2.97) (very low quality evidence), as well as to finasteride in two studies (MD 1.49, 95% CI -0.58 to 3.56 and MD 0.40, 95% CI -1.18 to 1.98) (low quality evidence).Although there was very low quality evidence of a difference in reduction of Ferriman-Gallwey scores for finasteride 5 mg to 7.5 mg daily versus placebo (MD -5.73, 95% CI -6.87 to -4.58), it was unlikely it was clinically meaningful. These results were reinforced by participants' assessments (RR 2.06, 95% CI 0.99 to 4.29 and RR 11.00, 95% CI 0.69 to 175.86). However, finasteride showed inconsistent results in comparisons with other treatments, and no firm conclusions could be reached.Metformin demonstrated no benefit over placebo in reduction of Ferriman-Gallwey scores (MD 0.05, 95% CI -1.02 to 1.12), but the quality of evidence was low. Results regarding the effectiveness of GnRH analogues were inconsistent, varying from minimal to important improvements.We were unable to pool data for OCPs with cyproterone acetate 20 mg to 100 mg due to clinical and methodological heterogeneity between studies. However, addition of cyproterone acetate to OCPs provided greater reductions in Ferriman-Gallwey scores.Two studies, comparing finasteride 5 mg and spironolactone 100 mg, did not show differences in participant assessments and reduction of Ferriman-Gallwey scores (low quality evidence). Ferriman-Gallwey scores from three studies comparing flutamide versus metformin could not be pooled (I² = 62%). One study comparing flutamide 250 mg twice daily with metformin 850 mg twice daily for 12 months, which reached a higher cumulative dosage than two other studies evaluating this comparison, showed flutamide to be more effective (MD -6.30, 95% CI -9.83 to -2.77) (very low quality evidence). Data showing reductions in Ferriman-Gallwey scores could not be pooled for four studies comparing finasteride with flutamide as the results were inconsistent (I² = 67%).Studies examining effects of hypocaloric diets reported reductions in BMI, but which did not result in reductions in Ferriman-Gallwey scores. Although certain cosmetic measures are commonly used, we did not identify any relevant RCTs. AUTHORS' CONCLUSIONS Treatments may need to incorporate pharmacological therapies, cosmetic procedures, and psychological support. For mild hirsutism there is evidence of limited quality that OCPs are effective. Flutamide 250 mg twice daily and spironolactone 100 mg daily appeared to be effective and safe, albeit the evidence was low to very low quality. Finasteride 5 mg daily showed inconsistent results in different comparisons, therefore no firm conclusions can be made. As the side effects of antiandrogens and finasteride are well known, these should be accounted for in any clinical decision-making. There was low quality evidence that metformin was ineffective for hirsutism and although GnRH analogues showed inconsistent results in reducing hirsutism they do have significant side effects.Further research should consist of well-designed, rigorously reported, head-to-head trials examining OCPs combined with antiandrogens or 5α-reductase inhibitor against OCP monotherapy, as well as the different antiandrogens and 5α-reductase inhibitors against each other. Outcomes should be based on standardised scales of participants' assessment of treatment efficacy, with a greater emphasis on change in quality of life as a result of treatment.

ALTERATIONS IN HYPOTHALAMIC CONTENT OF LUTEINIZING HORMONE RELEASING HORMONE AND PITUITARY RESPONSIVENESS ASSOCIATED WITH TESTICULAR REGRESSION INDUCED BY PINEAL RELATED TREATMENTS IN THE GOLDEN HAMSTER

The adult male golden hamster, when exposed to blinding (BL), short photoperiod (SP), or daily melatonin injections (MEL) demonstrates dramatic reproductive collapse. This collapse can be blocked by removal of the pineal gland prior to treatment. Reproductive collapse is characterized by a dramatic decrease in both testicular weight and serum gonadotropin titers. The present study was designed to examine the interactions of the hypothalamus and pituitary gland during testicular regression, and to specifically compare and contrast changes caused by the three commonly employed methods of inducing testicular regression (BL,SP,MEL). Hypothalamic LHRH content was altered by all three treatments. There was an initial increase in content of LHRH that occurred concomitantly with the decreased serum gonadotropin titers, followed by a precipitous decline in LHRH content which reflected the rapid increases in both serum LH and FSH which occur during spontaneous testicular recrudescence. In vitro pituitary responsiveness was altered by all three treatments: there was a decline in basal and maximally stimulatable release of both LH and FSH which paralleled the fall of serum gonadotropins. During recrudescence both basal and maximal release dramatically increased in a manner comparable to serum hormone levels. While all three treatments were equally effective in their ability to induce changes at all levels of the endocrine system, there were important temporal differences in the effects of the various treatments. Melatonin injections induced the most rapid changes in endocrine parameters, followed by exposure to short photoperiod. Blinding required the most time to induce the same changes. This study has demonstrated that pineal-mediated testicular regression is a process which involves dynamic changes in multiply-dependent endocrine relationships, and proper evaluation of these changes must be performed with specific temporal events in mind. ^

Historias de hormonas en Argentina : La obesidad de los niños y el diagnóstico precoz del embarazo en las décadas de 1930 y 1940

Este artículo aborda, desde una perspectiva de género, la producción de saberes sobre hormonas en Argentina, en las décadas de 1930 y 1940. Entendemos que un análisis histórico de las ideas científicas y las prácticas clínicas permite indagar en cómo éstas se entraman tanto con el escenario social del que forman parte como con los contextos institucionales donde se elaboran. Focalizaremos en las miradas de los endocrinólogos del Hospital de Niños de Buenos Aires sobre la obesidad en la infancia y el síndrome adiposo genital, y los debates en la Sociedad de Obstetricia y Ginecología de Buenos Aires sobre las técnicas de detección precoz del embarazo y la hormona gonadotropina coriónica

Historias de hormonas en Argentina : La obesidad de los niños y el diagnóstico precoz del embarazo en las décadas de 1930 y 1940

Este artículo aborda, desde una perspectiva de género, la producción de saberes sobre hormonas en Argentina, en las décadas de 1930 y 1940. Entendemos que un análisis histórico de las ideas científicas y las prácticas clínicas permite indagar en cómo éstas se entraman tanto con el escenario social del que forman parte como con los contextos institucionales donde se elaboran. Focalizaremos en las miradas de los endocrinólogos del Hospital de Niños de Buenos Aires sobre la obesidad en la infancia y el síndrome adiposo genital, y los debates en la Sociedad de Obstetricia y Ginecología de Buenos Aires sobre las técnicas de detección precoz del embarazo y la hormona gonadotropina coriónica

Historias de hormonas en Argentina : La obesidad de los niños y el diagnóstico precoz del embarazo en las décadas de 1930 y 1940

Este artículo aborda, desde una perspectiva de género, la producción de saberes sobre hormonas en Argentina, en las décadas de 1930 y 1940. Entendemos que un análisis histórico de las ideas científicas y las prácticas clínicas permite indagar en cómo éstas se entraman tanto con el escenario social del que forman parte como con los contextos institucionales donde se elaboran. Focalizaremos en las miradas de los endocrinólogos del Hospital de Niños de Buenos Aires sobre la obesidad en la infancia y el síndrome adiposo genital, y los debates en la Sociedad de Obstetricia y Ginecología de Buenos Aires sobre las técnicas de detección precoz del embarazo y la hormona gonadotropina coriónica

Influencia de la castración y la línea genética paterna sobre el rendimiento productivo y la calidad de la canal y de la carne en cerdos sacrificados a pesos elevados

El objetivo general de esta Tesis Doctoral fue estudiar la influencia del sexo, el método de castración de los machos y la línea genética paterna sobre la productividad y la calidad de la canal y de la carne en cerdos blancos sacrificados a pesos elevados con destino a la industria de los productos curados de calidad. En el experimento 1, se utilizaron 360 cerdos sacrificados a 125 kg de peso vivo (PV) para estudiar la influencia del sexo y la castración [machos inmunocastrados (MI), machos castrados quirúrgicamente (MC) y hembras enteras (HE)] de dos líneas genéticas paternas Large White (Top York y Tempo) sobre los rendimientos productivos y la calidad de la canal y de la carne. La línea materna utilizada fue Large White × Landrace en todos los casos. Los MI se inmunizaron contra el factor de liberación de gonadotropina (GnRF) mediante la utilización de Improvac a los 78 (16 d en prueba) y 126 (64 d en prueba y 48 d antes del sacrificio) d de edad. Cada uno de los 6 tratamientos experimentales fue replicado 6 veces (cuadra con 10 cerdos). Desde el inicio de la prueba hasta el día de la primera inyección con Improvac (62 a 78 d de edad) los MI y las HE crecieron menos (P < 0,001) que los MC sin que se observaran diferencias en el consumo medio diario de pienso (CMD). Los MC tuvieron peor eficiencia alimenticia que las HE con los MI mostrando valores intermedios (P < 0,01). Entre las dos inyecciones de Improvac (78 a 126 d de edad), los MI crecieron y comieron menos que los MC, mostrando las HE valores intermedios (P < 0,001). Los MI fueron más eficientes que las HE y ambos más eficientes que los MC (P < 0,001). Sin embargo, desde la segunda inyección de Improvac hasta el sacrificio (126 a 174 d de edad) los MI crecieron más y fueron más eficientes (P < 0,001) que las HE y los MC. Al final de la prueba, MI y MC crecieron más (P < 0,01) que HE. Asimismo, los MI fueron más eficientes (P < 0,001) pero presentaron menor rendimiento de canal (P < 0,001) que los MC y las HE. Por otro lado, los MI y las HE depositaron menos grasa dorsal que los MC (P < 0,001). Las hembras tuvieron mayor rendimiento de lomo y menos grasa intramuscular que MI y MC (P < 0,01). Asimismo, las HE tuvieron mayor rendimiento de jamón en fresco y perfilado que los MC con los MI mostrando valores intermedios (P < 0,05). Los cerdos híbridos procedentes de machos Tempo crecieron más (P < 0,001) que los procedentes de machos Top York, sin que se encontraran diferencias para el CMD o para la eficiencia alimenticia. Los híbridos de los cruces con Top York tuvieron mejores rendimientos de jamones frescos y perfilados (P < 0,05) pero menor rendimiento de lomo y menos grasa intramuscular que los cruces con Tempo (P < 0,01). En conclusión, los MI presentaron mejor eficiencia alimenticia, pero menor rendimiento de canal que los MC y las HE. El contenido en grasa intramuscular fue similar entre MC y MI y superior para ambos que para las HE. Los cruces procedentes de la línea paterna Tempo crecieron más y tuvieron mayor contenido en grasa intramuscular, pero un rendimiento en jamón perfilado ligeramente inferior al de los cruces procedentes de la línea paterna Top York. Se concluye que la inmunocastración de los machos es una alternativa viable a la castración quirúrgica para la producción de cerdos pesados destinados a la industria de los productos curados. Debido a su mayor potencial de crecimiento y mayor contenido en grasa intramuscular, los híbridos procedentes de la línea paterna Tempo presentan ventajas frente a los híbridos procedentes de la línea paterna Top York cuando se destinan a la industria de productos curados de calidad. En el experimento 2, se utilizaron 240 cerdos para comparar los rendimientos productivos y los parámetros de calidad de la canal de MI, MC y HE destinados a la industria de productos cárnicos curados procedentes del cruce de la línea materna Large White × Landrace con la línea genética paterna Duroc o Pietrain. Entre las 2 inyecciones de Improvac (87 a 137 d de edad), los MI y las HE crecieron menos que los MC (P < 0,01). Asimismo, los MI comieron menos pienso que las HE y ambos menos que los MC (2,33, 2,55 y 2,77 kg/d; respectivamente; P < 0,001). Como resultado, los MI fueron más eficientes que los MC y las HE (P < 0,001). Desde la segunda inyección de Improvac hasta el momento del sacrificio (137 a 164 d de edad), los MI fueron más eficientes que las HE y ambos más que los MC (0,346, 0,323 y 0,300, respectivamente; P < 0,001). Las diferencias observadas en este periodo entre los sexos en cuanto a rendimientos productivos fueron más pronunciadas en los cerdos procedentes de la línea paterna Pietrain que los de la línea Duroc (P < 0,05 para la interacción). En el global de la prueba (87 a 164 d de edad) el sexo no afectó al crecimiento en los cerdos procedentes de la línea paterna Duroc pero en los cerdos procedentes de la línea paterna Pietrain, los MI y los MC crecieron más que las HE (P < 0,05 para la interacción). Asimismo, los MI tuvieron mejor eficiencia alimenticia (0,406, 0,364 y 0,380, P < 0,001) y menor rendimiento de la canal (76,6, 78,1 y 78,8%; P < 0,001) que los MC y las HE. Las canales de las HE fueron más magras que las canales de los MC, con las canales de los MI mostrando valores intermedios (P < 0,01). El rendimiento en jamones y lomos fue mayor para las HE que para los MI y los MC (P < 0,001). El contenido en grasa intramuscular fue menor en las HE que en los MC, con los MI mostrando valores intermedios (3,5 vs. 3,9 y 3,7%; P < 0,05). Por otra parte, los híbridos procedentes de machos Duroc crecieron más rápido (1,167 vs. 0,986 kg/d; P < 0,001), consumieron más pienso (3,07 vs. 2,56 kg/d; P < 0,001) y tuvieron más grasa intramuscular (P < 0,001), pero menor rendimiento en jamones y lomos (P < 0,01) que los híbridos procedentes de machos Pietrain. Se concluye que los MI presentaron mejores productividades pero menores rendimientos de canal que MC y HE. El contenido en grasa intramuscular en el músculo longissimus dorsi fue menor para las HE que para los MC con valores intermedios para los MI. Los cruces procedentes de la genética paterna Duroc crecieron más y tuvieron más grasa intramuscular pero menos rendimiento de jamón que los cerdos procedentes de machos Pietrain. Por tanto, los MI deben ser preferidos a los MC y los cruces con la línea paterna Duroc deben ser preferidos a los cruces con Pietrain para producir canales cuando sus partes nobles están destinadas a la industria de productos cárnicos curados. En base a estos resultados, se concluye que la inmunocastración es una alternativa factible a la castración quirúrgica y que líneas genéticas paternas Tempo y Duroc son mejores para la producción de cerdo blanco pesado que las líneas Top York y Pietrain. Las interacciones entre el sexo y las líneas genéticas paternas estudiadas, sugieren que el resultado final depende en parte de la línea genética paterna utilizada. En cualquier caso, la inmunocastración es una alternativa factible a la castración quirúrgica para la producción de canales destinadas a la industria de los productos cárnicos curados. ABSTRACT The general aim of this PhD Thesis was to study the influence of sex, method of castration, and genetic background of the sire line on growth performance and carcass and meat quality merits of heavy white pigs destined to the dry-cured industry. In experiment 1, 360 pigs slaughtered at 125 kg of body weight were used to study the influence of sex and castration methodology [immunocastrated males (ICM), surgically castrated males (SCM), and intact females (IF)] of 2 terminal Large White sire lines (Top York and Tempo) on growth performance and carcass and meat quality. The female line was Large White × Landrace in all cases. The ICM pigs were immunized against gonadotropin-releasing factor with Improvac at 78 (16 d on trial) and 126 (64 d on trial and 48 d before slaughter) d of age. Each of the 6 treatments was replicated 6 times (10 pigs/pen). From the start of the experiment to the day of the first Improvac injection (62 to 78 d of age), ICM and IF grew slowlier (P < 0.001) than SCM but no differences in feed intake were detected. The SCM pigs had greater gain to feed ratio (G:F) than the IF with the ICM pigs being intermediate (P < 0.01). Between the 2 Improvac injections (78 to 126 d of age), the ICM pigs ate less feed (P < 0.001) and grew slowlier rate than the SCM pigs, with the growth of IF being intermediate. The ICM pigs were more efficient than the IF, and both were more efficient than the SCM pigs (P < 0.001). However, from the second Improvac injection to slaughter (126 to 174 d of age), the ICM pigs grew at a faster rate (P < 0.001) and were more efficient (P < 0.001) than the IF and the SCM pigs. Cumulatively, ICM and SCM pigs grew faster (P < 0.01) than IF and the ICM pigs were more efficient than the other two sexes (P < 0.001). However, the ICM pigs had reduced (P < 0.001) carcass yield compared with SCM and IF. The ICM and IF pigs also had less (P < 0.001) backfat depth than the SCM pigs. Intact females had higher (P < 0.01) loin yield but less intramuscular fat (P < 0.01) than ICM and SCM pigs and higher (P < 0.05) fresh and trimmed ham yields than SCM pigs, with ICM pigs being intermediate. Crossbreds from the Tempo sires grew faster (P < 0.001) than crossbreds from the Top York sires but no differences (P > 0.10) were detected for feed intake or feed efficiency. Crossbreds from the Top York sires had higher (P < 0.05) fresh and trimmed ham yields but less (P < 0.01) loin yield and intramuscular fat content than crossbreds from the Tempo sires. In conclusion, ICM pigs are more efficient, but have less carcass yield than SCM and IF pigs. The intramuscular fat content was lowest for the IF and similar for ICM and SCM pigs. Crossbreds from Tempo sires were heavier and had greater intramuscular fat content, but had less trimmed ham yield as compared with crossbreds from the Top York sires. Immunocastrated pigs can replace SCM pigs for the production of heavy pigs destined for the dry-cured industry. Because of increased carcass weight and the higher intramuscular content, crossbreds from Tempo sires may have an advantage over crossbreds from Top York sires for the dry-cured industry. In experiment 2, a total of 240 pigs were used to compare growth performance and carcass quality traits of immunocastrated males, surgically castrated males, and intact females of crossbreds from Large White × Landrace females and Duroc or Pietrain sires destined to the dry-cured industry. Between the 2 Improvac injections (87 and 137 d of age), ICM and IF pigs had lower average daily gain (ADG) than SCM pigs (P < 0.01). Also, ICM pigs ate less feed than IF and both type of pigs ate less than SCM pigs (2.33, 2.55, and 2.77 kg/d; P < 0.001). Consequently, ICM pigs had better G:F than SCM and IF (P < 0.001). From the second Improvac injection to slaughter (137 to 164 d of age), ICM pigs were more efficient than IF and both were more efficient than SCM pigs (0.346, 0.323, and 0.300 g/g; P < 0.001). The differences in growth performance among genders observed in this period were more pronounced for the Pietrain than for the Duroc crossbreds (P < 0.05 for the interaction). For the entire experimental period (87 to 164 d of age), gender did not affect ADG for Duroc crossbreds but for Pietrain crossbreds ICM and SCM had higher ADG than IF (P < 0.05 for the interaction). The ICM pigs had better feed efficiency (0.406, 0.364, and 0.380; g/g; P < 0.001) and lower carcass yield (76.6, 78.1, and 78.8%; P < 0.001) than SCM or IF. Carcasses from IF were leaner than carcasses from SCM with carcasses from ICM being intermediate (P < 0.01). Ham and loin (P < 0.001) yields were higher for IF than for ICM or SCM pigs. Intramuscular fat content was lower for IF than for SCM pigs with that of ICM pigs being intermediate (3.5 vs. 3.9 and 3.7%; P < 0.05). Cumulatively, crossbreds from Duroc sires had higher ADG (1.167 vs. 0.986 kg/d; P < 0.001) and average daily feed intake (3.07 vs. 2.56 kg/d; P < 0.001) and more intramuscular fat (P < 0.001) but less ham and loin yields (P < 0.01) than crossbreds from Pietrain sires. It is concluded that growth performance was better, but carcass yield lower, for ICM pigs than for SCM and IF. Intramuscular fat content in longissimus dorsi muscle was lower for IF than for SCM pigs with ICM pigs being intermediate. Crossbreds from Duroc sires grew faster and had more intramuscular fat but less ham yield than crossbreds from Pietrain sires. Therefore, ICM pigs should be preferred to SCM pigs, and Duroc crossbreds should be preferred to Pietrain crossbreds to produce carcasses destined to the production of primal cuts for the dry-cured industry. We conclude that immunocastration might be a sound alternative to surgical castration in pigs and that Tempo and Duroc might be better for the production of heavy pigs than Top York and Pietrain. The interactions reported between sex and genetic sire line, suggested that the benefits of immunocastration as an alternative to surgical castration might depend at least part on the sire line used. In any case, immunocastration is a good alternative to surgical castration for the production of carcasses destined to the dry-cured industry.

Induction of ovulation in rabbit does using purified nerve growth factor and camel seminal plasma

The presence of an ovulation-inducing factor (OIF) in the seminal plasma (SP) of several species with spontaneous and induced ovulation, including the rabbit, has been documented. Recent studies have demonstrated that the OIF in the SP of camels (SPCAM) is a nerve growth factor (β-NGF). The aim of this study was to determine if purified β-NGF from mouse submandibular glands or SPCAM could provoke ovulation induction in the rabbit doe. A total of 35 females were synchronized with 25 IU of equine chorionic gonadotropin (Serigan, Laboratorios Ovejero, Spain) and allocated into 4 groups. Forty-eight hours later (Day 0), does were given a single dose (IM) of 1 mL of saline solution (SS; n = 8); 1 mL of gonadorelin (GnRH; Inducel, Laboratorios Ovejero, Spain; n = 9); 24 µg of β-NGF (2.5S-NGF; Promega, USA; n = 10); or 1 mL of centrifuged raw camel SP (SPCAM; 127 pg mL–1 NGF; n = 8). After treatment, an empty catheter was introduced through the vagina to simulate the nervous/mechanical stimulus of coitus (4 animals per group). Plasma LH concentrations were determined in blood samples taken 30 min before treatment and at 0, 30, 60, 90, and 120 min after injection. Progesterone concentrations were assessed at 0 and 120 min and every 2 days until Day 6 after treatment. Concentrations of β-NGF in camel SP and hormone determinations were made by enzyme immunoassay. Ovulation rate (OR) was determined after euthanasia on Day 7.

Modulation of cognition-specific cortical activity by gonadal steroids: A positron-emission tomography study in women

There is considerable evidence from animal studies that gonadal steroid hormones modulate neuronal activity and affect behavior. To study this in humans directly, we used H215O positron-emission tomography to measure regional cerebral blood flow (rCBF) in young women during three pharmacologically controlled hormonal conditions spanning 4–5 months: ovarian suppression induced by the gonadotropin-releasing hormone agonist leuprolide acetate (Lupron), Lupron plus estradiol replacement, and Lupron plus progesterone replacement. Estradiol and progesterone were administered in a double-blind cross-over design. On each occasion positron-emission tomography scans were performed during (i) the Wisconsin Card Sorting Test, a neuropsychological test that physiologically activates prefrontal cortex (PFC) and an associated cortical network including inferior parietal lobule and posterior inferolateral temporal gyrus, and (ii) a no-delay matching-to-sample sensorimotor control task. During treatment with Lupron alone (i.e., with virtual absence of gonadal steroid hormones), there was marked attenuation of the typical Wisconsin Card Sorting Test activation pattern even though task performance did not change. Most strikingly, there was no rCBF increase in PFC. When either progesterone or estrogen was added to the Lupron regimen, there was normalization of the rCBF activation pattern with augmentation of the parietal and temporal foci and return of the dorsolateral PFC activation. These data directly demonstrate that the hormonal milieu modulates cognition-related neural activity in humans.