Luteinizing Hormone Secretion and Corticotropin-Releasing Factor Gene Expression in the Paraventricular Nucleus of Rhesus Monkeys Following Cortisol Synthesis Inhibition¹

Abstract

Corticotropin-releasing Factor (CRF) is an important inhibitory neuromodulator of GnRH/LH secretion, and mediates in part the inhibitory effects of stress on the hypothalamic-pituitary-gonadal axis. The purpose of the present study was to further investigate CRF's role in regulating LH secretion in primates. This was accomplished by examining LH secretion in ovariectomized rhesus monkeys (n = 7) following cortisol synthesis inhibition with metyrapone. Infusion of metyrapone (5 mg/kg per h) for 4 h decreased cortisol levels to less than 20% of controls while increasing ACTH approximately 10-fold. LH concentrations were not affected by this acute activation of the hypothalamic-corticotroph axis. In a second experiment, metyrapone was infused for 10 h before collecting serial blood samples every 15 min for 6 h. Although this protocol produced a sustained increase in ACTH, no apparent effect on pulsatile 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, and 72.5 +/- 6.2 ng/ml, respectively, in metyrapone pretreated monkeys. The same regimen of metyrapone infusion increased CRF messenger RNA levels in the paraventricular nucleus by approximately 33% (P < 0.0002). In a final experiment designed to examine the potential synergy between CRF and cortisol, the LH response to insulin-induced hypoglycemia was contrasted in saline and metyrapone pretreated monkeys. LH concentrations were reduced to approximately 40% of basal levels following insulin in both metyrapone and saline pretreated monkeys. Therefore, even though inhibition of cortisol synthesis leads to an increase in CRF messenger RNA in the paraventricular nucleus and a robust increase in ACTH secretion in rhesus monkeys, presumably due in part to increased neuroendocrine CRF secretion, LH secretion was not inhibited during either the acute or more chronic phase of corticotroph activation. Absence of LH inhibition was not due to low cortisol concentrations resulting from metyrapone because metyrapone did not prevent hypoglycemia-induced suppression of LH secretion. We conclude that increased neuroendocrine CRF secretion following metyrapone does not inhibit LH secretion under these conditions. Several explanations for this result are discussed.

Effects of GnRH immunization on the reproductive axis and thymulin

“…The regional discrepancy in immunoactive GnRH may be largely explained by the fact that the Arc that is the key area of the steroid hormone feedback regulation on GnRH (Yeo & Herbison 2014). In immunized male rats, the fairly low level of testosterone negatively feedback regulates the production of GnRH neurons in the Arc instead of the Pa and MPN, which contain many GnRH cell bodies to regulate other hypophysiotropic hormone releasing hormones besides GnRH (Van Vugt et al 1997, Rivalland et al 2006. Likewise, the release of GnRH was significantly suppressed via reduction in the conveyance of GnRH to its nerve terminals in the ME of immunized rats (Glanowska & Moenter 2015).…”

Putative drivers of adrenocortical activity in captive African lesser bushbaby (Galago moholi)

“…The more direct regulation of the HPGaxis occurs through the suppression of GnRH-expression neurons, by CRF, at signal transduction and transcription regulation levels (Kinsey-Jones et al 2006;Tellam et al 1998). Although the regulatory effect of CRF on the HPG-axis has been observed numerous times, instances exist where an increase in cortisol concentrations in non-human primates does not translate into suppression of reproductive function (Cameron 1997;Vugt et al 1997).…”