ABSTRACT

The effects of 4–6 days of food deprivation on the pituitary-testicular function of adult male rats were studied. Fasting decreased body weights on average by 23% (P<0·01) and those of seminal vesicles by 55% (P<0·01) in 4 days. No consistent changes were found in testicular and ventral prostate weights. The pituitary levels of gonadotrophin-releasing hormone (GnRH) receptors decreased by 50% (P<0·01). Serum and pituitary levels of LH, FSH and prolactin decreased by 25–50% (P<0·01 for all). Testicular and serum levels of testosterone decreased by 70–80%, testicular LH receptors by 26%, those of prolactin by 50% (P<0·01 for all), but those of FSH remained unaffected. Acute (2 h) stimulation by a GnRH agonist (buserelin, 10 μg/kg i.m.) resulted in similar LH, FSH and testosterone responses in the fasted and control animals, and human chorionic gonadotrophin (hCG) stimulation (30 IU/kg i.m.) in similar increases in testosterone. A 42% decrease was found in pituitary content of mRNA of the common α subunit (P<0·05), but the mRNAs of the LH- and FSH-β chains and prolactin were unaffected by fasting for 4 days. When the same mRNAs were measured after 6 days of fasting, the decrease of the mRNA of FSH-β also became significant (50%, P<0·01). In contrast, the mRNA of LH-β was increased twofold (P<0·01) at this time and serum LH levels were similar in control and starved animals. It is concluded that during short-term starvation of male rats: (1) the decrease in gonadotrophin and prolactin synthesis and secretion is first noticed on the level of translation (protein synthesis), and the mRNA levels of these hormones may respond more slowly to starvation, (2) decreased pituitary GnRH receptors indicate decreased GnRH release from the hypothalamus, (3)the gonadotrophin and prolactin loss results secondarily in decreased testicular androgen synthesis and LH and prolactin receptor levels, (4) no decrease occurs during starvation in acute gonadotrophin response to GnRH, or testicular testosterone response to hCG, (5) the primary response to starvation in male rat pituitary-testicular function is the loss of normal hypothalamic support of gonadotrophin and prolactin secretion, rather than direct nutritional effects on the pituitary and testis, and (6) when starvation is continued beyond 4 days, a recovery is seen in pituitary mRNA on the LH-β chain and in serum LH, most probably because the starvation-associated decrease serum testosterone is a more potent positive stimulus of LH synthesis than the direct hypothalamic-pituitary inhibition.

Journal of Endocrinology (1989) 121, 409–417

ABSTRACT

Direct effects of testosterone on gonadotrophins at the pituitary level were studied in intact and castrated immature (age 10 days) and mature (70 days) male rats. Gonadotrophin-releasing hormone action was blocked by treatment with a potent GnRH antagonist, Ac-d-pClPhe-d-pClPhe-d-Trp-Ser-Tyr-d-Arg-Leu-Arg-Pro-d-Ala-NH₂CH₃COOH (Ant; Organon 30276; 1·0 mg/kg body weight per day) injected subcutaneously. Silicone elastomer capsules were used for the testosterone treatment. Both treatments commenced on the day of orchiectomy and lasted for 7 days. In adult male rats Ant treatment suppressed serum testosterone from 9·5 ± 2·5 (s.e.m.) nmol/l to below the limit of detection (< 0·10 nmol/l; P < 0·01), and the testosterone implants reversed the decrease. Treatment with Ant decreased the pituitary content of FSH-β subunit mRNA in intact and orchiectomized rats to 14% of their respective controls (P < 0·01). These levels were increased to 80–81% of controls (not significant) in both groups by combined treatment with testosterone and Ant. Orchiectomy alone increased FSH-β subunit mRNA by 202% (P < 0·01). In intact immature rats Ant treatment decreased the level of pituitary FSH-β subunit mRNA to 21% (P<0·01), and a partial recovery (P < 0·01) to 42% of controls was observed with combined Ant + testosterone treatment. In contrast, in orchiectomized immature rats, where ANT decreased FSH-β subunit levels to 48% of controls (P < 0·01), testosterone was able to reverse these mRNA levels completely (114% of controls). No evidence for the direct pituitary effects of testosterone were found in the mRNA of the common α or LH-β subunits. In adult rats, the testicular inhibin α and β_A subunit mRNA levels were increased (P < 0·01) by Ant + testosterone compared with Ant-treated animals, but there were no differences in serum immunoreactive inhibin between any of the uncastrated adult groups. In intact immature rats, Ant + testosterone treatment increased (P < 0·01) inhibin β_A subunit mRNA levels compared with controls and Ant-treated animals. Ant decreased the level of peripheral inhibin immunoreactivity from 8·3 ± 2·0 U/ml to 2·1 ± 0·4 U/ml (P < 0·01) and testosterone reversed it to 5·8 ± 0·6 U/ml (not significant).

In conclusion, our observations indicated that testosterone is able to stimulate FSH gene expression and secretion directly in immature and adult rats, but the testosterone response is enhanced at both ages by orchiectomy, even more so in the immature rat. This may be explained by age differences in the contribution of testicular inhibin to the regulation of FSH synthesis and secretion at the pituitary level.

Journal of Endocrinology (1993) 137, 69–79

Abstract

The effects of 3-week treatment with increasing doses of epitestosterone (ET) on gonadotrophin gene expression and secretion, on testosterone and 5α-dihydrotestosterone (DHT) levels, and on the weight of testes and prostates, were studied in intact adult male rats. The hormones were delivered by means of silastic capsules of different lengths filled with the steroid. One group of rats received testosterone (T) instead of ET, to compare the results with previous studies concerning the testosterone effect. The controls were given capsules with glucose only. Treatment with ET, as well as with T, significantly reduced the weights of prostates. When the data from ET-treated rats and controls were combined, a significant negative correlation (P<0·001) was found between the weight of prostates and serum ET. T, in contrast to ET, also decreased significantly the weights of testes. ET treatment caused a significant reduction of serum T levels but only an insignificant decline of DHT levels, independent of the dose. Serum and pituitary (p) luteinizing hormone (LH) levels in the ET-treated rats did not change. Pituitary mRNA contents for the βLH subunit (βLH-mRNA) showed a dose-dependent significant increase, up to 170% (P<0·01), with ET treatment. pFSH decreased with the lowest ET (2 cm) dose (P<0·05), but no change was observed with the other doses. The mRNA for the common α-subunit also increased with the ET load. In conclusion, ET acts at several sites in the regulation of gonadotrophin formation and release. It enhances the steady-state mRNA levels of both gonadotrophins in the pituitary. At the same time, ET may act directly in the pituitary by inhibition of post-transcriptional events in LH synthesis. A direct inhibitory effect of ET at the hypothalamic level is also possible. The circulating levels of both gonadotrophins are thus the result of these composite effects.

Journal of Endocrinology (1994) 143, 353–358