The effects of oral administration of tamoxifen (a synthetic non-steroidal anti-oestrogen) at doses of 40, 200 or 400 micrograms kg-1 day-1 on the circulating concentrations of LH, FSH, prolactin, testosterone and oestradiol, weights of pituitary, testes, secondary sex organs and the fertility of adult male rats were determined. The drug was administered per os daily, for up to 90 days. The fertility of rats treated with tamoxifen for 60, 70, 80 or 90 days was assessed by allowing them to mate with normal female rats of proven fertility. Tamoxifen at 40 micrograms kg-1 day-1 reduced concentrations of testosterone in plasma but had no affect on LH, FSH, prolactin and oestradiol concentrations, and the weights of pituitary, testes, epididymides, ventral prostate and seminal vesicles. Tamoxifen at 40 micrograms kg-1 day-1 reduced potency, fecundity, the number of implantation sites, the fertility index and litter size. Tamoxifen at 200 and 400 micrograms kg-1 day-1 reduced the concentrations of LH and testosterone in plasma and the weights of testes and secondary sex organs compared with controls. Tamoxifen at 400 micrograms kg-1 day-1 was most effective in reducing the number of viable pups, the litter size (< or = 1) and the fecundity (20%). The potency of treated rats (a measure of the presence of an ejaculate) was significantly decreased when compared with controls, but copulation was apparently not affected as mated female rats showed a constant dioestrous phase. Histology of the testes revealed disorganization of the cytoarchitecture of the tubules with obliterated lumen.(ABSTRACT TRUNCATED AT 250 WORDS)

The dose-related effects of estradiol 17-beta at the doses 0.1 pg, 10 microg, 100 microg, 200 microg, 300 microg, 400 microg, 1,000 microg/kg/day were determined on sperm motility, potency, fertility parameters, serum levels of LH, FSH, PRL and testosterone, weights of testes and accessory sex organs, weights of pituitary and adrenal glands. The drug was administered daily via sc route for a period of 60 days. Dose-related effects on fertility parameters of the estradiol-treated male rats were ascertained by allowing them to mate with normal cycling female rats. Estradiol at 0.1 microg/kg/day dose significantly reduced sperm motility with no effects seen on potency or fecundity, serum LH, FSH, PRL or testosterone, weights of testes and accessory sex organs while pituitary weight increased. Estradiol at 10 microg/kg/day dose significantly reduced motility, serum LH, FSH, weights of testes and accessory sex organs, while pituitary weight increased with no effects seen on potency, fecundity, PRL or testosterone. Estradiol at 100-1,000 microg/kg/day dose significantly reduced motility, potency and fecundity, serum LH, FSH and testosterone, weights of testes and accessory sex organs while serum PRL and the weights of pituitary and adrenal glands increased significantly. Histology of the testes revealed disorganization of the cytoarchitecture in the seminiferous tubules, vacuolation, absence of lumen and compartmentalization of spermatogenesis. Estradiol withdrawal, testosterone propionate at 100 pg/kg/day or antiestrogen (tamoxifen citrate) at 400 microg/kg/day prevented the histological changes. It is conduded that estradiol reduces sperm motility even at a low dose. Low doses (<10 microg/kg/ day) appear to maintain whilst high doses (>10 microg/kg/day) reversibly disrupt spermatogenesis. Prevention of disruption by testosterone or antiestrogen indicates crosstalk between androgen and estrogen receptors in Sertoli cells. Loss of potency and fecundity also suggests effects on crosstalk between these receptors in other male reproductive organs.

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The underlying mechanisms in human infertility associated with hyperprolactinemia have yet to be established. Hyperprolactinemia is a known side-effect of fluphenazine, a broad spectrum, long-acting phenothiazine known to be D2 dopamine receptor antagonist. Dose-related effects of fluphenazine decanoate were ascertained on the fertility of 60-day treated, adult male rats. Significant increase in the serum levels of prolactin and decrease in the levels of LH and FSH were seen at doses of 1-3 mg/kg/day. No effect was evident on the serum testosterone (T) and estradiol. The tissue levels of Inhibins were not affected. The weights of testes, epididymides, seminal vesicles, ventral prostate, adrenal and pituitary glands were not affected. Testicular histology showed sloughing indicating the sensitivity of this parameter to FSH deficiency. Mating occurred within 10 days of cohabitation in the control and 1-2 mg/kg/day treated groups but delayed in the 3 mg/kg/day treated group with a significant effect on potency. Implantation sites, litter size and fertility index were significantly reduced at 2-3 mg/kg/day doses of fluphenazine. No effects however were seen on sperm counts or motility whereas morphological changes were apparent in the acrosome. Chromatin decondensation in vitro was enhanced and sperm chromatin structure assay revealed DNA denaturation. Hypothalamic tyrosine hydroxylase levels were increased in 1-3 mg/kg/day dose range. Hyperprolactinemic males sired fewer pups as compared to controls. Hypothalamic tyrosine hydroxylase was upregulated at all the doses. The antifertility effects of fluphenazine-induced hyperprolactinemia appeared to be unrelated to testosterone (T). In addition, FSH decrease might have affected the intrinsic sperm quality and thereby reduced litter size.

Diurnal variations and temporal coupling in the circulating levels of immunoactive and bioactive luteinizing hormone (LH) and prolactin (PRL), testosterone (T) and 17-beta-estradiol (E₂) in plasma of 6 healthy men (mean age 33 years) were studied. Each hormonal profile was analyzed for circadian amplitude, acrophase and nadir. Acrophases for immunoactive LH and T were coincident and ranged between clock hours 1 and 5. Acrophase for bioactive LH ranged between 9 and 12 h and was coincident with nadir for T. Acrophase for E₂ ranged between 15 and 18 h and was coincident with nadir for immunoactive LH (15–17 h). Acrophase for bioactive PRL and immunoactive PRL ranged between 20–23 and 23–4 h, respectively. The circadian amplitude for T showed a negative correlation coefficient with circadian amplitude of bioactive LH (alpha = -0.86) and positive correlation coefficient with circadian amplitude of immunoactive LH (alpha = 0.94). It is inferred that immunoactive LH may be a sensor of T concentration while bioactive LH may be actually involved in the feedback regulation of T secretion. It is suggested that PRL may have a key role in the regulation of LH secretion.