ENDOCRINE INTERACTION BETWEEN ZINC AND PROLACTIN - AN INTERPRETATIVE REVIEW

Zinc plays a very important role in animal and human metabolism. Nowadays, it is one of the most extensively studied trace element, since its sphere of action has been demonstrated to be very broad. From the biochemical standpoint, it controls more than 300 different enzymes, many of them involved with intermediary metabolism, DNA and RNA synthesis, gene expression, and immunocompetence. It also plays a significant role in hormonal homeostasis, since it can interact with almost all hormones. Zn2+ is closely related to the thyroid and steroid hormones, insulin, parathormone, and pituitary hormones, particularly prolactin (PRL). Zn2+ can inhibit PRL secretion within a range of physiologically and pharmacologically relevant concentrations. This property has raised the possibility of clinical applications of zinc. In this article, we review the Literature on the subject in an attempt to provide a comprehensible general view.

Puberty and growth rate in thoroughbred fillies

We measured progesterone and estradiol levels from birth to the beginning of adult life in 10 Thoroughbred fillies from the Equilia Stud Farm in Avare SP, Brasil. The animals were measured and weighed monthly for the determination of body development and of a possible correlation between the rate of weight and height gain and the onset of detectable sex hormone levels. Jugular blood was collected twice a week and stored at -20 degrees C until assay of progesterone by a solid phase RIA with a sensitivity of 0.32 nmol/L and of estradiol by liquid phase RIA adapted to low levels (3.67 pmol/L). The fillies were born with high serum levels of both hormones,which fell to undetectable levels by the first week of life. A variation in growth rate was observed, with the highest levels occuring from birth to the 3rd month of life, followed by a reduction until 15 mo of life, when fast growth was resumed. The monthly weight gain was 1.5% when the fillies reached puberty and 5.4% during the next month, (P<0.05, Friedman test). During this second period of accelerated growth after the beginning of progesterone production at detectable levels (above 0.318 nmol/L), the parameters of skeletal growth did not differ (P>0.05). The month of onset of puberty was the month of lowest weight gain in the life of the fillies, and it coincided with the highest insolation period. In conclusion, horses, like all other developed vertebrates, have a double pattern of development, with the acceleration observed at puberty depending on sex steroids, which in turn coincides with the highest insolation period. Gonadal activity characterized by serum progesterone levels was low from birth to the onset of puberty. After puberty the progesterone cycles were similar to those of adult animals with a mature hypothalamic-gonadal axis. (C) 1997 by Elsevier B.V.

PARTICIPATION OF OPIOID RECEPTORS IN THE MODULATION OF THE ANALGESIC RESPONSE BY ADRENAL AND GONADAL GLANDS

The involvement of opioid receptors in the analgesic response was evaluated by the tail-immersion test in simultaneously adrenalectomized and ovariectomized female Wistar rats (210-250 g). The reaction time (mean +/- SEM) for tail withdrawal from hot water decreased significantly 2 weeks after surgery (3.52 +/- 0.20 s) when compared to intact animals (6.09 +/- 0.23 s). Hormonal replacement with dexamethasone (50-mu-g/day) did not affect reaction time (3.38 +/- 0.19 s). However, this response was restored by combined adrenal and gonadal steroid substitution (estradiol 5-mu-g/day and progesterone 1.5-mu-g 6 h before the tests) therapy (5.11 +/- 0.45 s in animals treated with dexamethasone plus estradiol and 5.04 +/- 0.43 s in animals treated with dexamethasone plus estradiol plus progesterone). Naloxone (2 mg/kg) decreased the reaction time of animals treated with adrenal and gonadal steroids (5.11 +/- 0.45 vs 4.15 +/- 0.44 s and 5.04 +/- 0.43 vs 3.87 +/- 0.28 s, respectively, before and after naloxone) but failed to decrease it in rats treated with dexamethasone only (3.88 +/- 0.18 vs 4.34 +/- 0.25 s, before and after naloxone). These observations indicate that gonadal steroids are the most important steroid factors involved in the reaction time to tail immersion in hot water and confirm other reports that the opioid pathways modulating the neuronal circuitry require the presence of these hormones.

Effect of thermal conditioning during embryonic development on aspects of physiological responses of broilers to heat stress

The purpose of the present study was to investigate the effect of thermal conditioning, (through exposure to heat stress), during pre-hatch development on some physiological responses of post-hatch broilers to a post-natal heat stress challenge. Exposure to heat stress at this stage, we hope, may possibly induce epigenetic heat adaptation. Incubating eggs were exposed to temperature of 39.0degreesC for 2 h from Day 13 to 17 of incubation. At 33, 35, 37, 39, 41 and 43 d of age, the broilers hatched from these eggs were housed individually in open-circuit respiration cells. The climatic chambers were set to 22degreesC and increased to 30degreesC for 4 h. O-2 consumption and CO2 production of each chicken was monitored continuously in order to calculate the heat production. Blood samples were obtained before and during the 4 h heat stress. Thermal conditioning during incubation did not affect the plasma T-4, corticosterone, glucose, uric acid and CK concentrations. Temperature challenge, decreased plasma T-3 of broilers of both groups but the decrease was greater in pre-conditioned broilers compared with controls. A similar trend was observed for triglycerides. These changes did not affect total heat production. Since decreased T3 and triglyceride levels are part of the mechanisms for thermoregulation, these suggest that thermal conditioning during incubation can improve the broiler chicken capability for thermotolerance at later post-hatch age. (C) 2002 Elsevier B.V. Ltd. All rights reserved.

GLUCOCORTICOID-REGULATED GENE IN TRANSFORMED TO NORMAL PHENOTYPIC REVERSION

Glucocorticoid hormones modulate the actions of peptide growth factors and constitute important therapeutic tools as anti-inflammatory and anti-tumor agents. The C6 rat glioma cell line responds to glucocorticoids with changes in morphology and growth block. The hyper-responsive ST1 cell variant displays a dramatic phenotypic reversion under the influence of these hormones. Thus, the transformed and tumorigenic cells reversibly change to a normal and non-tumorigenic phenotype. In addition, the cells also produce a C-type retrovirus. We used poly A(+) mRNA from ST1 cells that had been treated with hydrocortisone to generate a cDNA library that was then screened, by differential hybridization,for glucocorticoid-responsive cellular sequences. The retroviral genomic RNA was used to generate a viral-specific probe. Cross hybridization led to the isolation of at least 4 cDNA clones of which 3 are cellular sequences and one corresponds to a retroviral gene. These clones were characterized by DNA sequencing and Northern blot hybridization analysis.

Central interaction between atrial natriuretic peptide and angiotensin II in the control of sodium intake and excretion in female rats

We investigated the effects of estrogen on sodium intake and excretion induced by angiotensin II (ANG II), atrial natriuretic peptide (ANP) or ANG II plus ANP injected into the median preoptic nucleus (MnPO). Female Holtzman rats weighing 250-300 g were used. Sodium ingestion and excretion 120 min after the injection of 0.5 mu l of 0.15 M NaCl into the MnPO were 0.3 +/- 0.1 ml (N = 12) and 29 +/- 7 mu Eq in intact rats, 0.5 +/- 0.2 ml (N = 10) and 27 +/- 6 mu Eq in ovariectomized rats, and 0.2 +/- 0.08 (N = 11) and 38 +/- 8 mu Eq in estrogen-treated ovariectomized (50 mu g/day for 21 days) rats, respectively. ANG II (21 mu M) injection in intact, ovariectomized, and estrogen-treated ovariectomized rats increased sodium intake (3.8 +/- 0.4, 1.8 +/- 0.3 and 1.2 +/- 0.2 ml/120 min, respectively) (N = 11) and increased sodium excretion (166 +/- 18, 82 +/- 22 and 86 +/- 12 mu Eq/120 min, respectively) (N = 11). ANP (65 mu M) injection in intact (N = 11), ovariectomized(N = 10)and estrogen-treated ovariectomized (N = 10) rats increased sodium intake (1.4 +/- 0.2, 1.8 +/- 0.3, and 1.7 +/- 0.3 ml/120 min, respectively) and sodium excretion (178 +/- 19, 187 +/- 9, and 232 +/- 29 mu Eq/120 min, respectively). Concomitant injection of ANG II and ANP into the MnPO of intact (N = 12), ovariectomized (N = 10) and estrogentreated ovariectomized (N = 10) rats caused smaller effects than those produced by each peptide given alone: 1.3 +/- 0.2, 0.9 +/- 0.2 and 0.3 +/- 0.1 ml/120 min for sodium intake, respectively, and 86 +/- 9, 58 +/- 7, and 22 +/- 4 mu Eq/120 min for sodium excretion, respectively. Taken together, these results demonstrate that there is an antagonistic interaction of ANP and ANG II on sodium intake and excretion, and that reproductive hormones affect this interaction.

Mispatterning in the ommatidia of Apis mellifera pupae treated with a juvenile hormone analogue

To further understand the function of morphogenetic hormones in honeybee eye differentiation, the alterations in ommatidial patterning induced by pyriproxyfen, a juvenile hormone (JH) analogue, were studied by scanning and transmission electron microscopy. Prepupae of prospective honeybee workers were treated with pyriproxyfen and the effects on ommatidial differentiation were described at the end of the pupal development. The results show that the entire ommatidia, i.e., the dioptric as well as the receptor systems, were affected by the JH analogue. The wave of ommatidial differentiation, which progresses from the posterior to the anterior region of the pupal eyes, was arrested. In treated pupae, the rhabdomeres only differentiated at the apical axis of the retinula, the secondary and tertiary pigment cells did not develop their cytoplasm protrusions, and the cone cell quartet did not pattern correctly. Simultaneously, an intense vacuolization was observed in cells forming ommatidia. In a previous study we showed that pyriproxyfen exerts an inhibition on pupal ecdysteroid secretion. In this sense, the arrested ommatidial differentiation in pyriproxyfen-treated pupae could be due to a secondary effect resulting from an alteration in pupal ecdysteroid titers. J. Morphol. 249:89-99, 2001. (C) 2001 Wiley-Liss, Inc.

Prolactin and zinc in dialysis patients

The objectives of the present study were to investigate the frequencies of hyperprolactinemia and hypozincemia in patients undergoing hemodialysis (HD) or continuous ambulatory peritoneal dialysis (CAPD), the associations between blood levels of zinc (Zn2+) and hormones, and dietary zinc intake amount and its relation to zincemia. We studied 28 patients (14 HD and 14 CAPD) who had their blood levels of Zn2+, prolactin (PRL), parathyroid hormone (PTH), and gonadotropins (LH, FSH) evaluated. Thirteen patients had dietary nutrient amounts evaluated from a 3-d nutritional record. Hyperprolactinemia occurred in 29% patients (HD = CAPD), hypozincemia in 62% (20% HD and 42% CAPD), and low dietary Zn2+ intake in 90% of patients. No correlation among blood concentration of Zn2+ and PRL, PTH, LH, and FSH were observed in the two modalities of dialysis or between zincemia and Zn2+ ingestion. We concluded that the occurrence of hyperprolactinemia and hypozincemia were not related to dialysis modality and that zincemia did not reflect the observed low dietary intake of Zn2+.

EFFECT OF TESTOSTERONE ON THE PRESSOR-RESPONSE TO COMMON CAROTID OCCLUSION IN GONADECTOMIZED CONSCIOUS MALE-RATS WITH LESION OF THE MEDIAN-EMINENCE

The influence of testosterone on the development of the pressor response to common carotid occlusion was investigated in control and median eminence-lesioned male rats. In control rats (N = 9), gonadectomy performed 21 days before the experiments reduced by 22% (from 51 +/- 2 to 40 +/- 2 mmHg) and treatment with testosterone (300-mu-g for 4 days before the measurements) increased the initial peak pressor response (from 51 +/- 2 to 57 +/- 2 mmHg) which depends on carotid innervation. The maintained response which is of central origin (probably ischemic) was less affected. In nongonadectomized rats (N = 6), lesions of the median eminence (6 days) decreased the initial peak by 19% (from 52 +/- 2 to 42 +/- 3 mmHg) and the maintained response by 56% (from 32 +/- 2 to 14 +/- 1 mmHg). Sham-operated rats served as controls. In gonadectomized animals (N = 6) the lesion reduced only the maintained response (from 23 +/- 2 to 11 +/- 1 mmHg). Testosterone supplementation restored the maintained response but did not alter the initial peak. These results indicate that the pressor response to common carotid occlusion in male rats is modulated by testosterone and that the depression in the maintained response caused by median eminence lesion can be reversed by steroid supplementation.

The effect of hetero- and homosexual experience and long-term treatment with fluoxetine on homosexual behavior in male rats

Introduction the selective serotonin reuptake inhibitors have become the most frequently prescribed drugs for the treatment of depression. Sexual side effects have been noted to occur with this treatment on heterosexual behavior in rats. Heterosexual experience facilitates sexual orientation of male rats and decreases the latencies to first mount and first intromission. on the other hand, homosexual behavior in male rats induced by female hormones has not been evaluated.Aim the objective of this work is to evaluate the effects of heterosexual and homosexual experience in male rats long-term treated with fluoxetine (FLX) on homosexual hormone-induced behavior.Materials and Methods Male rats were treated with FLX or saline solution (10 mg/kg for 65 days). At days 36, 50, and 65 of the treatment, the rats were evaluated for homosexual behavior. Other rats treated with FLX or saline solution for 60 consecutive days were submitted to heterosexual behavior at 14, 21, and 28 days of the treatment. After this, they were orquiectomized and homosexual hormone-induced behavior was observed at 45 and 60 days of the treatment.Results (1) Only treatment with FLX did not affect the homosexual behavior. (2) the homosexual experience facilitated the homosexual behavior mainly on the animals from the control group. (3) the heterosexual experience facilitated the homosexual behavior on both groups.Conclusions Only long-term administration of FLX does not interfere with the homosexual behavior in male rats. The homosexual and the heterosexual experience facilitated the homosexual behavior on the control and experimental groups. We suggested that learning aspects related to sexual behavior are responsible by these results.

Clinical features and genetic analysis of four Brazilian kindreds with resistance to thyroid hormone

Objective Resistance to thyroid hormone (RTH) is a dominantly inherited syndrome of reduced tissue responsiveness to thyroid hormone usually due to mutations located in the ligand-binding domain and adjacent hinge region of the thyroid hormone receptor beta (TR beta). In the present report we describe the clinical and laboratory characteristics and the genetic analysis of patients with this rare disorder from a Brazilian population.Patients Four unrelated Brazilian families with diagnosis of RTH were studied. Age at diagnosis varied from 14 months to 29 years.Results All affected individuals were clinically euthyroid, except for one patient who presented immediately after birth with hyperthyroidism. All individuals had tachycardia and goitre, elevated concentrations of free thyroid hormones and reduced sensitivity to thyroid hormone. Direct sequencing analysis of the TR beta gene revealed four previously reported mutations: c.949G -> A, c.1313G -> A, c.1357C -> A and c.1358dupC in families A, B, C and D, respectively.Conclusion the present report shows that the frequent mutations described in the thyroid hormone receptor worldwide are also present in the Brazilian population, which is characterized by a variable ethnic background.

THE ESSENTIAL ROLE OF ZINC IN GROWTH

Zinc is known to play a relevant role in growth and development. The basic mechanisms of action of this trace element are intimately linked to the structure and action of countless enzymes involved in many different metabolic processes. In this respect, when zinc specifically acts on cartilage growth it is involved in multiple enzymatic reactions which make this a multifactorial event. Thus, we may divide the actions of zinc into three distinct types: 1) action on taste and smell acuity, appetite regulation, and food consumption and regulation; 2) action on DNA and RNA synthesis stimulating a) cell replication and differentiation of chondrocytes, osteoblasts and fibroblasts; b) cell transcription culminating in the synthesis of somatomedin-C (liver), alkaline phosphatase, collagen and osteocalcin (bone), and c) protein, carbohydrate and lipid metabolism, that is intimately related to the mechanisms of smell, taste, appetite, and food consumption and utilization; 3) action on hormonal mediation by participating in a) GH synthesis and secretion in somatomammotroph cells, b) the action of GH on liver somatomedin-C production, and c) somatomedin-C activation in bone cartilage. In addition to these multiple functions, zinc also interacts with other hormones somehow related to bone growth such as testosterone, thyroid hormones, insulin, and vitamin D-3.On the basis of the above considerations, we conclude that the integration of these mechanisms contributes to the perfect physiological functioning of bone. Tn the presence of zinc deficiency, this homeostasis is impaired, causing the weight-height deficiency detected in several species studied, the human species in particular.

Studies of natural-killer-cells in pregnancy-induced hypertension

The number and activity of natural killer (NK) cells were studied in 20 patients with pregnancy-induced hypertension (PIH), 15 uncomplicated pregnant women and 16 healthy non-pregnant women, All the pregnant women were primigravidae and were evaluated during the third trimester of gestation. Peripheral blood NK cells were detected with monoclonal antibodies by indirect immunofluorescence and cytotoxic activity was measured using a single-cell assay against K562 target cells. Hypertensive pregnant women had an increased number of circulating NK cells associated with a significant decrease of NK activity, the cytotoxic activity was significantly lower in normal pregnant and PIH women when compared with non-pregnant controls. The onset of immature NK cells in peripheral blood and the impairment of their cytotoxic activity in PIH patients may be associated with hormones and immunosuppressive substances produced by tissues occurring at the maternal-fetal interface.

The effect of timing of thermal conditioning during incubation on embryo physiological parameters and its relationship to thermotolerance in adult broiler chickens

Previously, we reported that thermal conditioning at 39degreesC on days 13-17 of incubation of broiler eggs enabled thermotolerance during post-hatch growth (J. Therm. Biol. 28 (2003) 133). Tolerance to a temperature of 30degreesC was accompanied by changes in thyroid hormones and metabolic parameters. In the current study, we determined the mechanism of epigenetic heat adaptation during embryonic age by measuring blood physiological parameters that may be associated with the ultimate effects of thermal conditioning. Hatching eggs from Ross breeders were subjected to heat treatment of 39degreesC at days 13, 14, 15, 16 and 17 of incubation for 2 h per day. Control eggs were incubated at 37.6degreesC. Samples of eggs were withdrawn on each day of thermal conditioning and at internal pipping (IP) to obtain blood samples from embryos. The remaining eggs were weighed at day 18 and transferred to hatchers. The timing of IP, external pipping (EP) and hatching were monitored every 2 h. At hatch, chicks were weighed and hatchability was determined. Blood samples were obtained from samples of day-old chicks. T3, T4, corticosterone, pCO(2), pO(2) levels were determined in the blood. Blood pH was measured and T3/T4 ratios were calculated. Heat conditioning significantly increased corticosterone and pO(2) levels and blood pH but depressed pCO(2) at day 14. These were followed by a significant depression of T4 level on day 15. Remarkably, at day 16, all these parameters were back to normal as in the control embryos. Hatching was delayed by thermal conditioning probably as a result of the depressed corticosterone levels at IP. Hatchability was also lower in the heat-treated group but 1-day old chick weights were comparable to those of the controls. The result suggests that epigenetic thermal conditioning involves changes in these physiological parameters and probably serve as a method for epigenetic temperature adaptation since the same mechanisms are employed for coping with heat during post-embryonic growth. It also suggests that days 14-15 may be the optimal and most sensitive timing for evoking this mechanism during embryonic development. The adverse effects of heat treatment observed in this study may have been due to the continued exposure to heat until day 17. Fine-tuning thermal conditioning to days 14-15 only may improve these production parameters. (C) 2003 Elsevier Ltd. All rights reserved.