Abstract

Short-term starvation suppresses the pituitary-testicular function in rats, evidently through inhibition of gonadotrophin-releasing hormone (GnRH) release. However, when gonadotrophin secretion is strongly enhanced, e.g. after castration, starvation does not suppress gonadotrophins. To test whether the time since castration affects the pituitary response to starvation, adult male rats were totally deprived of food for five days (only water allowed) immediately (acute castration) or two weeks after castration (chronic castration). The pituitary contents of GnRH receptors were decreased by starvation in sham-operated animals, unaffected in acutely castrated rats, but increased in chronically castrated animals, in comparison with appropriate controls (P<0·01). Castration per se increased steady-state mRNA levels of the common α-chain and the LH and FSH β-chains in all groups studied. The only consistent effect of starvation on these parameters was the 1·7 to 2-fold increase in the pituitary content of LH β-subunit mRNA in acutely and chronically castrated rats (P<0·01). Starvation alone suppressed LH secretion, acute castration eliminated this effect, but in chronically castrated rats, the starvation effect was stimulatory. Starvation did not affect FSH secretion in sham-operated and acutely castrated rats, but after chronic castration, the effect was stimulatory. In conclusion, the overall effect of starvation on gonadotrophins shifts gradually after castration from suppression, in sham-operated rats, to stimulation, in chronically castrated animals. Parallel changes in pituitary GnRH receptors suggest similar changes in GnRH secretion. Hence, starvation has both negative and positive effects on the GnRH-gonadotrophin-axis. The negative effect is evidently androgen-dependent and dominates in testes-intact animals. After chronic castration, only the positive, non-androgen dependent, stimulatory effect remains.

Journal of Endocrinology (1994) 143, 209–219

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