Leptin as a link between the immune system and kidney-related diseases: leading actor or just a coadjuvant?

Food intake and nutritional status modify the physiological responses of the immune system to illness and infection and regulate the development of chronic inflammatory processes, such as kidney disease. Adipose tissue secretes immune-related proteins called adipokines that have pleiotropic effects on both the immune and neuroendocrine systems, linking metabolism and immune physiology. Leptin, an adipose tissue-derived adipokine, displays a variety of immune and physiological functions, and participates in several immune responses. Here, we review the current literature on the role of leptin in kidney diseases, linking adipose tissue and the immune system with kidney-related disorders. The modulation of this adipose hormone may have a major impact on the treatment of several immune- and metabolic-related kidney diseases.

Optimizing rabbit production under heat stress: cage density and cage size during fattening, and breeding system and water quality on rabbit does

The aim of this work was to evaluate different management strategies to optimize rabbit production under chronic heat stress. To achieve it, three trials were conducted. In the first trial, to find the optimal cage density in tropical very dry forest condition, were measured growth performance, mortality rate, injured animals and carcass performance over an initial population of 300 cross-breed rabbits of New Zealand, California, Butterfly, Dutch and Satin, weaned at 30 days (535 ± 8 g, standard error). Treatments evaluated were: 6, 12, 18 and 24 rabbits/m2 (3, 6, 9 and 12 rabbits/cage, respectively, each cage of 0.5 m2). The maximal temperature-humidity index indicated a severe heat stress from weaning to 2.2 kg body weight (experimental time). At the end of experimental period 10, 20, 30 and 30 rabbits from the treatments of 6, 12, 18 and 24 rabbits/m2, respectively, were slaughtered and carcass performance recorded. Average daily gain and feed intake decreased by 0.31 ± 0.070 and 1.20 ± 0.25 g, respectively, per each unit that the density increased at the beginning of the experiment (P = 0.001). It increased the length of the fattening period by 0.91 ± 0.16 d (P = 0.001) per each unit of increment of density. However, rabbit production (kg/m2) increased linear and quadratically with the density (P < 0.008). Animals housed at the highest density compared to the lower one tended to show a higher incidence of ringworm (68.9 vs 39.4%; P = 0.075), injured animals (16.8 vs 3.03%; P = 0.12) and mortality (20.5 vs 9.63%; P = 0.043). The proportion of scapular fat (P = 0.042) increased linearly with increasing levels of density. Increasing density reduced linearly dorsal length (P = 0.001), and reduced linear and quadratically drip loss percentage (P = 0.097 and 0.018, respectively). In the second trial, 46 nulliparous rabbit does (23 clipped and 23 unclipped) with a BW of 3.67 ± 0.05 kg (s.e.) were used to evaluate heat stress and circadian rhythms comparing unclipped and clipped rabbit does, and to study if a more extensive breeding system increase litters performance at weaning without impairing rabbit doe performance,. Rectal temperature, feed and water 4 intake were recorded for 24 h. Rabbit does were mated 7 d after circadian measurements, and randomly assigned to two breeding systems. Control (C): mated at 14 d after parturition + litter weaned at 35 d of age. Extensive (E): mate at 21 after parturition + litter weaned at 42 d of age. The first three cycles were evaluated concerning to rabbit doe and litter performance. Two hundred twenty eight weaned rabbits, were divided into two cage sizes: 0.5 and 0.25 m2 with same density (16 rabbit/m2) and growing performance was recorded. Farm and rectal temperatures were minimal and feed and water intake maximal during the night (P < 0.001). Unclipped rabbit does showed higher rectal temperature (P = 0.045) and lower feed intake respect to clipped does (P = 0.019) which suggest a lower heat stress in the latter. Kits weaned per litter was reduced by 33% (P=0.038) in C group. This reduction was more important in the 2nd and 3rd cycles compared to the first (P ≤ 0.054). Rabbit doe feed efficiency tended to decrease in E respect C group (P = 0.093), whereas it was impaired from the first to the third cycle by 48% (P = 0.014). Growing rabbits from the E group were heavier at weaning (by 38%. P < 0.001), showed a higher feed intake (+7.4%) and lower feed efficiency (-8.4%) throughout the fattening period (P ≤ 0.056) respect to C group. Cage size had minor influence in growing performance. In the third trial, forty five non pregnant and non lactating rabbit does (21 nulliparous and 24 multiparous) were assigned randomly to farm water and to potable water to study if a water quality improvement can affect positively rabbit doe response to heat stress during pregnancy and lactation. A transponder was implanted in each animal to record subcutaneous temperature at 07:30 and 14:30 h. Experimental period extended from pregnancy (with no lactation) to the next lactation (until day 28). Body temperature and milk production were recorded daily, and body condition, feed and water intake weekly. Water quality did not affect any trait (P ≥ 0.15). Pregnant rabbit does were classified as does that weaned (W: 47%), not weaned (NW: 44%) or those pregnant that did not deliver (NB: 9%). Body temperature and feed intake decreased during pregnancy (P ≤ 0.031), but water intake remained constant. In this period body temperature decreased with metabolic weight (P ≤ 0.009). In W and NW does, 5 from mating to birth energy and protein balance impaired (P≤0.011). Body temperature of W does tended to be the lowest (P ≤ 0.090). Pregnancy length and total number of kits born tended to be longer and higher in NW than in W does (P = 0.10 and 0.053, respectively). Kit mortality at birth and from birth to 14 d of lactation was high, being worse for NW than for W does (97 vs. 40%; P<0.001). Body temperature during lactation was maximal at day 12, and milk production increased it (P ≤ 0.025). . In conclusion, in our heat stress conditions densities higher than 18 rabbits/m2 (34 kg/m2) at the end of fattening, are not recommended despite cage size, gestation and lactation productivity impaired not only when lactation is extended and along successive reproductive cycles but also due to a reduced embryo/kit survival and finally water quality improvement did not attenuate negative effect of heat stress. RESUMEN El propósito de éste trabajo fue evaluar diferentes estrategias de manejo para optimizar la producción de conejos bajo estrés térmico. Para lo cual se desarrollaron tres experimentos. En el primer experimento, para encontrar el número óptimo de gazapos por m2 de jaula durante el cebo en condiciones de bosque muy seco tropical, se estudiaron los rendimientos durante el cebo, mortalidad, animales lesionados y rendimiento de la canal sobre una población inicial de 300 conejos mestizos de Nueva Zelanda, California, Mariposa, Holandés y Satin, destetados a los 30 días de edad (535 ± 8g, error estándar). Los tratamientos evaluados fueron: 6, 12, 18 y 24 conejos/m2 (3, 6, 9 y 12 conejos/jaula, respectivamente, en jaulas de 0.5 m2). Durante el período experimental (destete a 2.2 kg de peso vivo), se observaron valores de THI correspondientes con un estrés térmico severo (THI max. De 31 a 35). Al final del período experimental, 10, 20, 30, y 30 conejos de los tratamientos con densidades de 6, 12, 18 y 24 conejos/m2, respectivamente, fueron sacrificados y su canal fue valorada. El promedio de la ganancia diaria y el consumo de alimento disminuyeron en 0.31 ± 0.070 y 1.20 ± 0.25 g, respectivamente, por cada unidad de incremento en la densidad al inicio del experimento (P=0.001). Esto alargó el período de engorde en 0.91 ± 0.16 d (P=0.001) por cada unidad de incremento de la densidad. Sin embargo, la producción de conejos (kg/m2) aumentó lineal y cuadráticamente con la densidad (P<0.008). Los animales alojados en las mayores densidades en comparación con el resto tendieron a mostrar una mayore incidencia de tiña (68.9 vs 39.4%; P=0.075), de cantidad de animales heridos (16.8 vs 3.03%; P=0.12), así como de mortalidad (20.5 vs 9.63%; P=0.043). El aumento en la densidad aumentó linealmente la proporción de grasa escapular (P=0.042) y redujo linealmente la longitud dorsal (P=0.001), y lineal y cuadráticamente el porcentaje de pérdida por goteo (P=0.018). En el segundo experimento, 46 conejas nulliparas (23 rasuradas y 23 no rasuradas) con un peso vivo de 3.67 ± 0.05 kg (e.e.) fueron usadas para evaluar el estrés 8 térmico y los ritmos circadianos comparando conejas rasuradas o no, y estudiar si un sistema de crianza más extensivo mejora el desempeño de la camada al destete sin perjudicar la productividad de la coneja. Durante 24 h se midió la temperatura rectal, consumo de alimento y de agua. Las conejas fueron montadas 7 días después, y distribuidas en dos sistemas de crianza. El control (C): monta a 14 días posparto y destete a 35 d de edad. El extensivo (E): monta a 21 días posparto y destete a 42 d de edad. Se controló la productividad de la coneja y la camada durante los tres primeros ciclos. Doscientos veintiocho gazapos fueron distribuidos en dos tamaños de jaulas (0.5 y 0.25 m2) con la misma densidad (16 conejos/m2) y se controlaron sus rendimientos productivos. Durante la noche se observaron los valores mínimos para la temperatura ambiental y rectal, y los máximos para consumo de alimento y agua (P< 0.001). Las conejas no rasuradas mostraron mayor temperatura rectal (P=0.045) y menores valores de consumo de alimento con respecto a las conejas rasuradas (P=0.019), lo que sugiere un menor estrés térmico en las últimas. El número de gazapos destetados por camada se redujo en 33% (P=0.038) en el grupo C. Este comportamiento se acentuó en el 2do y 3er ciclo en comparación con el primero (P≤0.054). La eficiencia alimenticia de las conejas tendió a disminuir en el grupo E con respecto al grupo C (P=0.093), dicha tendencia se acentúa del primer al tercer ciclo en un 48% (P=0.014). Los gazapos en fase de crecimiento provenientes del grupo E fueron más pesados al momento del destete (en 38% P<0.001), mostrando un mayor consumo de alimento (+7.4%) y menor eficiencia alimenticia (-8.4%) a lo largo del engorde (P≤0.056) con respecto al grupo C. El tamaño de la jaula tuvo una mínima influencia en el comportamiento durante el crecimiento de éstos gazapos. En el tercer experimento, cuarenta y cinco conejas no gestantes ni lactantes (21 nulíparas y 24 multíparas) se les asignó al azar agua dos tipos de agua: común de la granja y agua potable, con el fin de estudiar si una mejora en la calidad del agua puede afectar positivamente la respuesta de la coneja al estrés térmico durante la gestación y la lactancia. Se les implantó un transponder para registrar la temperatura subcutánea a las 7:30 y a las 14:30 h. El período experimental se extendió desde la gestación (sin 9 lactancia) hasta la lactanción consecutiva (hasta los 28 días). La temperatura corporal y la producción de leche se controlaron diariamente, y la condición corporal, consumo de agua y alimento, semanalmente. La calidad del agua no afectó a ninguna variable (P≥0.15). Las conejas preñadas fueron clasificadas como conejas que destetaron (W: 47%), que no destetaron (NW:44%) o aquellas que no parieron (NB: 9%). La temperatura corporal y consumo de alimento disminuyeron durante la gestación (P≤0.031), mientras que el consumo de agua se mantuvo constante. La temperatura corporal descendió con el peso metabólico durante la gestación (P≤0.009). El balance de energía y proteína disminuyó desde la monta al parto para las conejas W y NW (P≤0.011). Durante la gestación la temperatura corporal tendió a ser menor en las conejas W (P≤0.090). La longitud de la gestación y el número total de gazapos nacidos tendieron a ser mayores en conejas NW que en conejas W (P=0.10 y 0.053, respectivamente). La mortalidad de los gazapos al parto y del parto a los 14 días de lactancia fue alta, siendo peor para las conejas NW que para las W (97 vs 40%; P<0.001). Durante la lactancia la temperatura corporal alcanzó su valor máximo para el día 12, y la producción de leche indujo un incremento en la misma (P≤0.025). En conclusión, en nuestras condiciones de estrés térmico y sin importar el tamaño de la jaula, no se recomiendan densidades mayores a 18 conejos/m2 (34 kg/m2) al final del engorde. La productividad de la gestación y la lactancia disminuyen cuando la lactancia es mayor y se suceden varios ciclos reproductivos seguidos. Esto se debe al efecto negativo del estrés térmico sobre la vitalidad y supervivencia del embrión/gazapo. La mejora de la calidad del agua atenuó el efecto negativo del estrés térmico. Las conejas más productoras parece que son aquéllas que consiguen manejar mejor el estrés térmico.

Bok is a pro-apoptotic Bcl-2 protein with restricted expression in reproductive tissues and heterodimerizes with selective anti-apoptotic Bcl-2 family members

In the intracellular death program, hetero- and homodimerization of different anti- and pro-apoptotic Bcl-2-related proteins are critical in the determination of cell fate. From a rat ovarian fusion cDNA library, we isolated a new pro-apoptotic Bcl-2 gene, Bcl-2-related ovarian killer (Bok). Bok had conserved Bcl-2 homology (BH) domains 1, 2, and 3 and a C-terminal transmembrane region present in other Bcl-2 proteins, but lacked the BH4 domain found only in anti-apoptotic Bcl-2 proteins. In the yeast two-hybrid system, Bok interacted strongly with some (Mcl-1, BHRF1, and Bfl-1) but not other (Bcl-2, Bcl-xL, and Bcl-w) anti-apoptotic members. This finding is in direct contrast to the ability of other pro-apoptotic members (Bax, Bak, and Bik) to interact with all of the anti-apoptotic proteins. In addition, negligible interaction was found between Bok and different pro-apoptotic members. In mammalian cells, overexpression of Bok induced apoptosis that was blocked by the baculoviral-derived cysteine protease inhibitor P35. Cell killing induced by Bok was also suppressed following coexpression with Mcl-1 and BHRF1 but not with Bcl-2, further indicating that Bok heterodimerized only with selective anti-apoptotic Bcl-2 proteins. Northern blot analysis indicated that Bok was highly expressed in the ovary, testis and uterus. In situ hybridization analysis localized Bok mRNA in granulosa cells, the cell type that underwent apoptosis during follicle atresia. Identification of Bok as a new pro-apoptotic Bcl-2 protein with restricted tissue distribution and heterodimerization properties could facilitate elucidation of apoptosis mechanisms in reproductive tissues undergoing hormone-regulated cyclic cell turnover.

Analysis of the reproductive system of female vampire squid

Analysis of the reproductive system of female vampire squid to determine reproductive strategy and fecundity of vampire squid, accessioned in the Santa Barbara Museum of Natural History and collected in 60, 70s from off southern California.

The threat of predictable and unpredictable pain: Differential effects on central nervous system processing?

Central nervous system performance is disrupted by pain and by the threat of pain. It is not known whether disruption caused by the threat of pain is dependent on the likelihood of pain occurring. We hypothesised that when a painful stimulus is possible but unpredictable central nervous system performance is reduced, but when the pain is predictable and unavoidable it is not. Sixteen healthy subjects performed a reaction time task during predictable and unpredictable conditions (100% and 50% probability of pain, respectively). Group data showed increased reaction time with the threat of pain by 50 ms (95% Cl 16 to 83 ms) for the predictable condition and 46 ms (95% CI 12 to 80 ms) for the unpredictable condition (p < 0.01 for both), but there was no difference between predictable and unpredictable conditions (p = 0.41). However, individual data showed that there was a differential effect in 75% of subjects (p < 0.05 for all) and that there was a greater effect of predictable pain for some subjects and a greater effect of unpredictable pain for others. Reaction time was related to reported anxiety (r = 0.49, p = 0.02 for both conditions). The predictability of a painful stimulus may have a differential effect on central nervous system performance within individuals, but anxiety about the impending pain appears to be important in determining this effect.

Floral structure, breeding system and fruit-set in the threatened sub-shrub Tetratheca juncea Smith (Tremandraceae)

Tetratheca juncea Smith (Tremandraceae) has undergone a range contraction of approx. 50 km in the last 100 years and is now listed as a vulnerable sub-shrub restricted to the central and north coast regions of New South Wales, Australia. There are approx. 250 populations in a 110 km north-south distribution and populations are usually small with fewer than 50 plants/clumps. The reproductive ecology of the species was studied to determine why seed-set is reportedly rare. Flowers are bisexual, odourless and nectarless. Flowers are presented dependentally and there are eight stamens recurved around the pistil. Anthers are poricidal, contain viable pollen and basally contain a deep-red tapetal fluid that is slightly oily. Thus flowers are presented for buzz pollinators, although none were observed at flowers during our study. The species was found to be facultatively xenogamous with only one in 50 glasshouse flowers setting seed autogamously, i.e. without pollinator assistance. Field studies revealed fertile fruit in 24 populations but production varied significantly across sites from exceedingly low (0.6 fruits per plant clump) to low (17 fruits per plant clump). Fruit-set ranged from 0 to 65%, suggesting that pollen vectors exist or that autogamy levels in the field are variable and higher than glasshouse results. Fruit production did not vary with population size, although in three of the five populations in the south-west region more than twice as much fruit was produced as in populations elsewhere. A moderately strong relationship between foliage volume and fruit : flower ratios suggests that bigger plants may be more attractive than smaller plants to pollinators. A review of Tetratheca pollination ecology revealed that several species are poorly fecund and pollinators are rare. The habitat requirements for Tetratheca, a genus of many rare and threatened species, is discussed. (C) 2003 Annals of Botany Company.

The renin-angiotensin system and male reproduction: new functions for old hormones

The blood-borne renin-angiotensin system (RAS) is known best for its role in the maintenance of blood pressure and electrolyte and fluid homeostasis. However, numerous tissues show intrinsic angiotensin-generating systems that cater for specific local needs through actions that add to, or differ from, the circulating RAS. The male reproductive system has several sites of intrinsic RAS activity. Recent focus on the epididymis, by our laboratories and by others, has contributed important details about the local RAS in this tissue. The RAS components have been localized morphologically and topographically; they have been shown to be responsive to androgens and to hypoxia; and angiotensin has been shown to influence tubular, and consequently, fluid secretion. Components of the RAS have also been found in the testis, vas deferens, prostate and semen. Angiotensin II receptors, type 1 and, to a lesser extent, type 2 are widespread, and angiotensin IV receptors have been localized in the prostate. The roles of the RAS in local processes at these sites are still uncertain and have yet to be fully elucidated, although there is evidence for involvement in tubular contractility, spermatogenesis, sperm maturation, capacitation, acrosomal exocytosis and fertilization. Notwithstanding this evidence for the involvement of the RAS in various important aspects of male reproduction, there has so far been a lack of clinical evidence, demonstrable by changes in fertility, for a crucial role of the RAS in male reproduction. However, it is clear that there are several potential targets for manipulating the activity of the male reproductive system by interfering with the locally generated angiotensin systems.

Cognitive disorders and neurogenesis deficits in Huntington's disease mice are rescued by fluoxetine

Huntington's disease (HD) is a neurodegenerative disorder caused by an expanded CAG trinucleotide repeat encoding an extended polyglutamine tract in the huntingtin protein. Affected individuals display progressive motor, cognitive and psychiatric symptoms (including depression), leading to terminal decline. Given that transgenic HD mice have decreased hippocampal cell proliferation and that a deficit in neurogenesis has been postulated as an underlying cause of depression, we hypothesized that decreased hippocampal neurogenesis contributes to depressive symptoms and cognitive decline in HD. Fluoxetine, a serotonin-reuptake inhibitor commonly prescribed for the treatment of depression, is known to increase neurogenesis in the dentate gyrus of wild-type mouse hippocampus. Here we show that hippocampal-dependent cognitive and depressive-like behavioural symptoms occur in HD mice, and that the administration of fluoxetine produces a marked improvement in these deficits. Furthermore, fluoxetine was found to rescue deficits of neurogenesis and volume loss in the dentate gyrus of HD mice.

Male reproductive tactics and female choice in the solitary, promiscuous bridled nailtail wallaby (Onychogalea fraenata)

Several behavioral studies of large, gregarious, and sexually dimorphic macropods have shown that males form dominance hierarchies and large males have the highest reproductive success. The bridled nailtail wallaby (Onychogalea fraenata) is a smaller and strongly sexually dimorphic macropod, but is also highly solitary and males do not form dominance hierarchies that are maintained temporally or spatially. Genetic studies of paternity have shown that large males are the most reproductively successful and only one-quarter of males sire offspring at any one time. The aim of this study was to investigate the tactics that males adopt to secure access to females at the time of estrus and to investigate whether females can influence which males have access to them. This study was conducted using 2 wild, free-ranging populations of bridled nailtail wallabies. Females in estrus were located and observed. and the total number of males present, the relative weight rank of each mate, and interactions between individuals were recorded. Females showed a preference for large males and incited male-male competition when the group of males present was large. Unlike other dimorphic macropods, fights among males were rare and were restricted to males of similar size. Large males gained access to females by guarding and following them closely and threatening other males who attempted to gain access. Smaller males spent less time with females, suggesting that small males may leave multimale groups in an attempt to locate unguarded females. Given the solitary nature of this species and the lack of a stable dominance hierarchy to influence male reproductive success. mate searching and mate guarding may be important male reproductive tactics in this species.

A pathology of the animal spirits - the clinical neurology of Thomas Willis (1621-1675) Part I - Background, and disorders of intrinsically normal animal spirits

Thomas Willis (1621-1675), author of the classical work Cerebri Anatome (1664), was arguably the father of the modem era of neurology. As compared with his neuroanatomy, relatively little attention has been paid to Willis' clinical neurology, as described in his Pathologiae Cerebri (1667) and Do Anima Brutorum (1672), where he gave a structured account of disease of the nervous system as it was known in his day. His account was largely derived from personal observations and not from traditional authorities and was based around his concept of the animal spirits, a fictitious entity in many ways analogous to the present day idea of the nerve impulse. This concept allowed him to develop a pathology of the animal spirits which embraced the whole content of the clinical neurology and psychiatry of his times. The anatomical and physiological background to Willis! concepts of animal spirit dysfunction, and those disorders he regarded as due to disturbed function of intrinsically normal animal spirits (mainly headache, disorders of consciousness, apoplexy and palsy) are dealt with in the present paper. The disorders he attributed to inherently abnormal animal spirits are considered in a second part of the paper. (C) 2002 Elsevier Science Ltd. All eights reserved.

Semi-determinate Growth Habit Adjusts The Vegetative-to-reproductive Balance And Increases Productivity And Water-use Efficiency In Tomato (solanum Lycopersicum).

Tomato (Solanum lycopersicum) shows three growth habits: determinate, indeterminate and semi-determinate. These are controlled mainly by allelic variation in the SELF-PRUNING (SP) gene family, which also includes the florigen gene SINGLE FLOWER TRUSS (SFT). Determinate cultivars have synchronized flower and fruit production, which allows mechanical harvesting in the tomato processing industry, whereas indeterminate ones have more vegetative growth with continuous flower and fruit formation, being thus preferred for fresh market tomato production. The semi-determinate growth habit is poorly understood, although there are indications that it combines advantages of determinate and indeterminate growth. Here, we used near-isogenic lines (NILs) in the cultivar Micro-Tom (MT) with different growth habit to characterize semi-determinate growth and to determine its impact on developmental and productivity traits. We show that semi-determinate genotypes are equivalent to determinate ones with extended vegetative growth, which in turn impacts shoot height, number of leaves and either stem diameter or internode length. Semi-determinate plants also tend to increase the highly relevant agronomic parameter Brix×ripe yield (BRY). Water-use efficiency (WUE), evaluated either directly as dry mass produced per amount of water transpired or indirectly through C isotope discrimination, was higher in semi-determinate genotypes. We also provide evidence that the increases in BRY in semi-determinate genotypes are a consequence of an improved balance between vegetative and reproductive growth, a mechanism analogous to the conversion of the overly vegetative tall cereal varieties into well-balanced semi-dwarf ones used in the Green Revolution.

Correlation Between The Friedman Staging System And The Upper Airway Volume In Patients With Obstructive Sleep Apnea.

This study was designed to evaluate the correlation between computed tomography findings and data from the physical examination and the Friedman Staging System (FSS) in patients with obstructive sleep apnea (OSA). We performed a retrospective evaluation by reviewing the medical records of 33 patients (19 male and 14 female patients) with a mean body mass index of 30.38 kg/m(2) and mean age of 49.35 years. Among these patients, 14 presented with severe OSA, 7 had moderate OSA, 7 had mild OSA, and 5 were healthy. The patients were divided into 2 groups according to the FSS: Group A comprised patients with FSS stage I or II, and group B comprised patients with FSS stage III. By use of the Fisher exact test, a positive relationship between the FSS stage and apnea-hypopnea index (P = .011) and between the FSS stage and body mass index (P = .012) was found. There was no correlation between age (P = .55) and gender (P = .53) with the FSS stage. The analysis of variance test comparing the upper airway volume between the 2 groups showed P = .018. In this sample the FSS and upper airway volume showed an inverse correlation and were useful in analyzing the mechanisms of airway collapse in patients with OSA.

Multifunctional role of steroidogenic factor 1 and disorders of sex development

Disorders of sex development (DSD) involve several conditions that result from abnormalities during gonadal determination and differentiation. Some of these disorders may manifest at birth by ambiguous genitalia; others are diagnosed only at puberty, by the delayed onset of secondary sexual characteristics. Sex determination and differentiation in humans are processes that involve the interaction of several genes such as WT1, NR5A1, NR0B1, SOX9, among others, in the testicular pathway, and WNT4, DAX1, FOXL2 and RSPO1, in the ovarian pathway. One of the major proteins in mammalian gonadal differentiation is the steroidogenic nuclear receptor factor 1 (SF1). This review will cover some of the most recent data on SF1 functional roles and findings related to mutations in its coding gene, NR5A1.