The enzyme 5alpha-reductase (5alpha-R) is present in many mammalian tissues, including the brain. The physiological importance of 5alpha-R in the brain derives from its capability to convert testosterone (T) to a more potent androgen, dihydrotestosterone (DHT), and to convert progesterone and deoxycorticosterone (DOC) to their respective 5alpha-reduced derivatives, precursors of allopregnanolone and tetrahydroDOC, potent allosteric modulators of the gamma-aminobutyric acid receptor (GABA(A)-R). 5alpha-R occurs as two isoforms, 5alpha-R type 1 (5alpha-R1) and 5alpha-R type 2 (5alpha-R2). We studied the effects of T and DHT on the mRNA levels of both 5alpha-R isozymes in the prefrontal cortex of the adult rat, using an accurate and precise method that combines the high specificity of one-step quantitative RT-PCR with the sensitivity of capillary electrophoresis. Our results demonstrate that both isozymes of 5alpha-R are expressed in the cerebral cortex of adult rats. The gene expression of 5alpha-R type 2 is under the positive control of T and DHT. The gene that codes for 5alpha-R type 1 is not constitutive, because its expression is negatively regulated by T and DHT. These results open up a new research line that may lead to a better understanding of the role of 5alpha-R isozymes in the physiology of the central nervous system.

Previous studies relating hormone and cytokine concentrations in follicular fluid to oocyte fertilizability were flawed by the uncertainty about the actual oocyte maturity status at the time of recovery and by the possible contribution of the male factor to failures of conventional in-vitro fertilization. This is the first study in which oocyte maturity was assessed immediately after recovery and only mature oocytes were selected for treatment by intracytoplasmic sperm injection. Fertilization outcomes were related to follicular fluid concentrations of 17beta-oestradiol, progesterone, follicle stimulating hormone, luteinizing hormone (LH), growth hormone (GH), prolactin (PRL), interleukin-1 (IL-1) and tumour necrosis factor-alpha (TNF alpha). Those oocytes that subsequently showed normal fertilization were harvested from follicles with higher concentrations of progesterone, GH, PRL, IL-1 and TNF alpha as compared with those of oocytes that failed to fertilize. Among the normally fertilized oocytes, low GH concentrations were associated with the failure of cleavage and with poor morphology of cleaving embryos, whereas rapidly cleaving embryos developed from oocytes recovered from follicles with high concentrations of LH and IL-1. These data suggest important roles for GH, IL-1 and TNF alpha, and of residual LH after pituitary suppression, as positive regulators of the final phase of oocyte intrafollicular development.

In males of seasonally breeding species, testes undergo a severe involution at the end of the breeding season, with a major volume decrease due to massive germ-cell depletion associated with photoperiod-dependent reduced levels of testosterone and gonadotropins. Although it has been repeatedly suggested that apoptosis is the principal effector of testicular regression in vertebrates, recent studies do not support this hypothesis in some mammals. The purpose of our work is to discover alternative mechanisms of testis regression in these species. In this paper, we have performed a morphological, hormonal, ultrastructural, molecular, and functional study of the mechanism of testicular regression and the role that cell junctions play in the cell-content dynamics of the testis of the Iberian mole, Talpa occidentalis, throughout the seasonal breeding cycle. Desquamation of live, nonapoptotic germ cells has been identified here as a new mechanism for seasonal testis involution in mammals, indicating that testis regression is regulated by modulating the expression and distribution of the cell-adhesion molecules in the seminiferous epithelium. During this process, which is mediated by low intratesticular testosterone levels, Sertoli cells lose their nursing and supporting function, as well as the impermeability of the blood-testis barrier. Our results contradict the current paradigm that apoptosis is the major testis regression effector in vertebrates, as it is clearly not true in all mammals. The new testis regression mechanism described here for the mole could then be generalized to other mammalian species. Available data from some previously studied mammals should be reevaluated.

The high incidence of prostate cancer (PCa) and benign prostatic hypertrophy (BPH) in elderly men is a cause of increasing public health concern. In recent years, various environmental endocrine disruptors, such as bisphenol A (BPA), have been shown to disrupt sexual organs, including the prostate gland. However, the mechanisms underlying these effects remain unclear. Because androgens and estrogens are important factors in prostate physiopathology, our objective was to examine in rat ventral prostate the effects of adult exposure to BPA on 5α-Reductase isozymes (5α-R types 1, 2, and 3) and aromatase, key enzymes in the biosynthesis of dihydrotestosterone and estradiol, respectively. Adult rats were subcutaneously injected for four days with BPA (25, 50, 300, or 600 µg/Kg/d) dissolved in vehicle. Quantitative RT-PCR, western blot and immunohistochemical analyses showed lower mRNA and protein levels of 5α-R1 and 5α-R2 in BPA-treated groups versus controls but higher mRNA levels of 5α-R3, recently proposed as a biomarker of malignancy. However, BPA treatment augmented mRNA and protein levels of aromatase, whose increase has been described in prostate diseases. BPA-treated rats also evidenced a higher plasma estradiol/testosterone ratio, which is associated with prostate disease. Our results may offer new insights into the role of BPA in the development of prostate disease and may be of great value for studying the prostate disease risk associated with exposure to BPA in adulthood.

- The effects of acute alcohol intoxication (AAI) on the pituitary-gonadal axis hormones, and the possible contribution of pituitary-adrenal axis hormones, beta-endorphin and prolactin to alcohol-induced dysfunction of pituitary-gonadal axis hormones were studied in adult men and women. Blood samples were drawn from adults of both sexes who arrived at the emergency department with evident behavioural symptoms of drunkenness (AAI) or from adult volunteers with nil consumption of alcohol (controls). Our results demonstrated that AAI produces a high increase in plasma prolactin, corticotropin (adrenocorticotropic hormone, ACTH), and cortisol in adults of both sexes, a decrease in luteinizing hormone levels only in men, an increase in dehydroepiandrosterone-sulphate (DHEAS) and a contradictory behaviour of testosterone according to gender, with increased plasma testosterone in women and a decrease in men. ACTH and prolactin correlated positively with cortisol, DHEAS and testosterone in women, which suggests that prolactin and ACTH could contribute to stimulated adrenal androgen production. In contrast, the decrease in testosterone and increase in beta-endorphin in men suggests that AAI could have an inhibitory effect on testicular testosterone, perhaps mediated by beta-endorphin. Our results suggest that the effect of alcohol on pituitary-gonadal axis hormones in humans could depend on the gender and degree of sexual maturity of the individual.

Teenage drinking is a cause of growing concern in industrialized countries, where almost 35% of alcohol drinkers are under 16 years old. Increased anxiety, irritability, and depression among adolescents may induce them to seek the anxiolytic and rewarding properties of alcohol. We studied the effects of acute alcohol intoxication (AAI) on the plasma levels of progesterone and allopregnanolone in female adolescents. Blood samples were drawn from female adolescents who arrived at the emergency department. One study group was formed by those who arrived with evident behavioral symptoms of AAI and the other by those arriving for mild trauma (contusions, sprains) after no consumption of alcohol (controls). Our results demonstrate that AAI significantly increases serum progesterone and allopregnanolone levels in both follicular and luteal phases of the ovarian cycle. Since alcohol and allopregnanolone positively modulate gamma-aminobutyric acid type A (GABA A ) receptors, allopregnanolone may play a major role in the anxiolytic and rewarding effects of alcohol, either directly or by influencing the sensitivity of GABA A -receptors to alcohol.

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This approach could be of great value for the study of prostate diseases in humans and would allow study at the transcriptional level of the effects of drugs that inhibit either or both of these isozymes.