EFFECT OF REPEATED ACTIVIN-A TREATMENT ON THE ACTIVITY OF THE HYPOTHALAMIC-PITUITARY-GONADAL AXIS OF THE ADULT MALE-RAT

The present study was undertaken to determine whether recombinant acti vin-A increases mRNA levels of the peptide GnRH, and whether this phen omenon correlates with increased FSH and/or LH release. One acute s.c. injection of activin-A (120 mu g/kg body weight) to adult male rats w as found to significantly (p < 0.01) increase plasma FSH levels, with no detectable changes in LH or testosterone (T) release. Similarly, th ere were no significant differences between GnRH mRNA values measured in the medial preoptic area of the hypothalamus. When activin-A was ad ministered s.c. every 8 h for seven consecutive treatments, similar re sults were obtained for gonadotropin release; in addition, we observed a significant (p < 0.01) up-regulation of hypothalamic GnRH mRNA leve ls. The administration of activin-A intracerebroventricularly (i.c.v., 6 mu g/rat) according to the same chronic schedule also produced a si gnificant (p < 0.01) increase in FSH levels, as well as a modest, but detectable, elevation in LH concentrations, and a large augmentation o f T secretion. In contrast, there were no changes in steady-state GnRH mRNA concentrations. Collectively, these results show that both the s ystemic (s.c.) and the central (i.c.v.) injection of activin-A stimula tes FSH secretion. While we had originally thought that the lack of re sponse of hypothalamic GnRH neurons to i.c.v. activin injections might have been due to increased steroid feedback, the observation that com parable results were obtained in both intact and castrated rats does n ot support this hypothesis. One possibility is that the previously rep orted stimulatory influence of i.c.v. activin-A treatment on neurons t hat manufacture corticotropin-releasing factor, and consequently on ci rculating catecholamine concentrations, may have increased testicular activity independently of changes in pituitary function.