Rapid Direct Effects of Castration and Androgen Treatment on Luteinizing Hormone-Releasing Hormone-Induced Luteinizing Hormone Release in the Phenobarbital-Treated Male Rat: Examination of the Roles Direct and Indirect Androgen Feedback Mechanisms Might Play in the Physiological Control of Luteinizing Hormone Release*

Publisher Website
Google Scholar
Abstract
Adult male rats, given phenobarbital (PB) to suppress their endogenous LH-releasing activity, were used to test whether orchidectomy and dihydrotesterone (DHT) treatment and withdrawal could act acutely to modify the pituitary LH release response to exogenous LHRH infusion. When LHRH was infused at a constant rate of 15 or 45 ng/h beginning immediately after orchidectomy, castrates and sham-castrated controls responded similarly for up to 18 h. However, when the LHRH infusion rate was abruptly changed from 15 to 45 ng/h 4 h postoperatively, castrates developed greater serum LH levels than uncastrated controls. Castration (the withdrawal of testicular feedback signals) appeared to have increased the ability of the pituitary to respond to an increment in the LHRH infusion rate. This effect of orchidectomy was reduced in rats given DHT by sc implantation at the time of castration, using doses of DHT equal to or less than those needed to prevent the orchidectomyinduced increase in circulating LH in the absence of PB treatment. When DHT implants which had been used to suppress spontaneous LH release during the initial 24 h after orchidectomy were removed, a 2- to 3-fold increase in pituitary responsiveness to LHRH ensued within 4 h, appreciably sooner than the spontaneous LH secretory response to orchidectomy in a rat with a functioning hypothalamus, which involves a 6- to 8-h lag period. Although effects of castration and DHT treatment were not seen during periods of constant rate LHRH infusion which began immediately after the steroid manipulation, they did become evident if the start of such an infusion was delayed until 3 h after castration. In this situation (in which the deferred onset of infusion was analogous to a step increment in an ongoing infusion), frequent blood sampling showed that the initial responses of the two groups of rats were indistinguishable and that the difference in responsiveness developed during the infusion. Therefore, the steroidal influences on the pituitary during the period preceding the onset of LHRH infusion did not modify the initial response to LHRH. They did modify the response amplification which developed during the second hour of continuous LHRH infusion. Similar response amplification has been seen previously in female rats, where it was attributed to LHRH self-priming. Although the direct androgen feedback mechanism revealed by these experiments appears to be both rapid and sensitive enough to play a role in the physiological regulation of LH release, it does not appear that it could ordinarily operate independently of an indirect (brain mediated) feedback mechanism. In the PB-treated rat, effects attributable to direct feedback were only observed after there had been an increase in exogenous LHRH stimulation. Extrapolation to events in the normal rat suggests that direct androgen feedback, although it might alter pituitary responsiveness to an appropriate stimulus, would not actually alter LH release until that stimulus had been supplied. In the absence of an exogenous stimulus, direct androgen feedback effects on LH release would have to await development of a feedback-mediated change in endogenous LHreleasing activity.