LUTEINIZING-HORMONE SECRETION AND CORTICOTROPIN-RELEASING FACTOR GENE-EXPRESSION IN THE PARAVENTRICULAR NUCLEUS OF RHESUS-MONKEYS FOLLOWINGCORTISOL SYNTHESIS INHIBITION

Corticotropin-releasing Factor (CRF) is an important inhibitory neurom odulator of GnRH/LH secretion, and mediates in part the inhibitory eff ects of stress on the hypothalamic-pituitary-gonadal axis. The purpose of the present study was to further investigate CRF's role in regulat ing LH secretion in primates. This was accomplished by examining LH se cretion in ovariectomized rhesus monkeys (n = 7) following cortisol sy nthesis inhibition with metyrapone. Infusion of metyrapone (5 mg/kg pe r h) for 4 h decreased cortisol levels to less than 20% of controls wh ile increasing ACTH approximately 10-fold. LH concentrations were not affected by this acute activation of the hypothalamic-corticotroph axi s. In a second experiment, metyrapone was infused for 10 h before coll ecting serial blood samples every 15 min for 6 h. Although this protoc ol produced a sustained increase in ACTH, no apparent effect on pulsat ile LH secretion compared with saline controls was observed. Mean LH ( +/- SEM) levels calculated for consecutive 2-h increments were 87.6 +/ - 9.2 (0-2 h) 82.1 +/- 5.5 (2-4 h), and 80.7 +/- 4.8 (4-6 h) ng/ml in saline pretreated animals compared with 83.6 +/- 4.9, 79.8 +/- 5.8, an d 72.5 +/- 6.2 ng/ml, respectively, in metyrapone pretreated monkeys. The same regimen of metyrapone infusion increased CRF messenger RNA le vels in the paraventricular nucleus by approximately 33% (P < 0.0002). In a final experiment designed to examine the potential synergy betwe en CRF and cortisol, the LH response to insulin-induced hypoglycemia w as contrasted in saline and metyrapone pretreated monkeys. LH concentr ations were reduced to approximately 40% of basal levels following ins ulin in both metyrapone and saline pretreated monkeys. Therefore, even though inhibition of cortisol synthesis leads to an increase in CRF m essenger RNA in the paraventricular nucleus and a robust increase in A CTH secretion in rhesus monkeys, presumably due in part to increased n euroendocrine CRF secretion, LH secretion was not inhibited during eit her the acute or more chronic phase of corticotroph activation. Absenc e of LH inhibition was not due to low cortisol concentrations resultin g from metyrapone because metyrapone did not prevent hypoglycemia-indu ced suppression of LH secretion. We conclude that increased neuroendoc rine CRF secretion following metyrapone does not inhibit LH secretion under these conditions. Several explanations for this result are discu ssed.