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.

Investigations were undertaken to study the differential modulation of LH, FSH and PRL secretion by testosterone (T) using whole pituitary (PI) or pituitary-hypothalamus coincubates (PHC) as in vitro constructs. PI and PHC from intact and castrated rats were incubated with or without T thrice, for 24 h each, (24 h x 3, total incubation period 72 h). The spent media was replenished every 24 h. At the end of 72 h, a few of the pituitary glands were challenged with 10 nM LHRH for 4 h. The spent media and pituitary glands were analyzed for LH, FSH and PRL using specific RIAs. Incubation of PI or PHC from intact rats with T stimulated the release of LH and FSH but inhibited the release of PRL. T had no effect on the intrapituitary contents of LH but inhibited intrapituitary contents of FSH and PRL, as compared to controls incubated without T. Castration increased intrapituitary contents of LH and FSH with concomitant decrease in PRL levels. Incubation of PI or PHC from castrated rats with T inhibited intrapituitary contents of LH to intact pituitary levels, while PRL levels were further reduced instead of being ameliorated. It is concluded that PI or PHC can be used as convenient in vitro models to monitor the effect of castration or of T modulation of pituitary and hypothalamus functions. T does not affect the synthesis of LH at the gonadotroph level but facilitates the regulation of intracellular LH and FSH levels. It is postulated that T inhibits the synthesis of FSH/PRL at the gonadotroph/lactotroph levels.

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