Modulation of gonadotropin secretion at the pituitary level by testosterone in gonadotropin-releasing hormone-treated male rats during food deprivation.

Testosterone (T) inhibits the synthesis and secretion of FSH and LH by decreasing the secretion of GnRH from the hypothalamus. However, T is also able to stimulate FSH gene expression and synthesis at the pituitary level when the release or action of GnRH is blocked. In the present study, we analyzed whether the positive effect of T on pituitary FSH could also be brought about during food restriction, which represents a model of suppressed GnRH secretion. We also wanted to learn whether this positive effect could be detected if GnRH pulsatility is maintained by exogenous injections. Adult male rats were subjected to various combinations of the following treatments: 1 ) implantation of silastic capsules containing T for Days 0-4 of the experiment, 2) starvation for Days 1-4 of the experiment, and 3) GnRH-treatment at 2-h intervals (500 ng/kg BW) for Days 3-4. The combined treatments were as follows: 1) control, 2) only starvation, 3) only GnRH, 4) starvation + GnRH, 5) only T, 6) starvation + T, 7) GnRH + T, and 8) starvation + GnRH + T (n = 12/group; two independent experiments). Serum FSH level was decreased 20% by starvation (p < 0.01), but no decrease was observed when the starving animals were treated with T. GnRH treatment increased serum FSH in both ad libitum-fed and starving animals to 266% and 333% of the respective control values (bothp < 0.01). When T was added to these treatments, the increases in serum FSH were smaller, 219% and 272%, respectively (p < 0.01 vs. respective groups without T). The FSH[ mRNA levels also increased in the GnRH-treated animals (1.6- to 2.5fold; p < 0.01), but the effect was not significantly affected by T. Serum LH was decreased to the same extent by starvation, by T, and by their combination (76-86%, p < 0.01 for all). GnRH increased serum LH in ad libitum-fed and starving rats 7.3-fold and 33.1-fold, respectively (p < 0.01 in both). T suppressed the stimulatory effect of GnRH on serum LH and pituitary mRNAs of LHO and common ca-chain in fed rats (p < 0.01), whereas such a T effect was not demonstrated in starving and GnRH-treated animals. In conclusion, the present study demonstrates that T has a direct stimulatory effect on FSH secretion in animals when the endogenous GnRH secretion is suppressed by food restriction. In contrast, it inhibits FSH secretion in controls and when GnRH pulsatility is maintained by exogenous treatment (control and starved rats). Hence, T has a 2-fold effect on FSH secretion at the pituitary level, stimulating in the absence of GnRH and inhibiting when GnRH effect persists. The suppressive effect of T on GnRH-stimulated LH secretion is lost during starvation.