The Central Effect of β-Endorphin and Naloxone on the Expression of GnRH Gene and GnRH Receptor (GnRH-R) Gene in the Hypothalamus, and on GnRH-R Gene in the Anterior Pituitary Gland in Follicular Phase Ewes

Abstract

The effect of prolonged intermittent infusion of beta-endorphin or naloxone into the third cerebral ventricle in ewes during the follicular phase of the estrous cycle on the expression of GnRH gene and GnRH-R gene in the hypothalamus and GnRH-R gene in the anterior pituitary gland was examined by Real time-PCR. Activation of micro opioid receptors decreased GnRH mRNA levels in the hypothalamus and led to complex changes in GnRH-R mRNA: an increase of GnRH-R mRNA in the preoptic area, no change in the anterior hypothalamus and decrease in the ventromedial hypothalamus and stalk/median eminence. In beta-endorphin treated ewes the levels of GnRH-R mRNA in the anterior pituitary gland also decreased significantly. These complex changes in the levels of GnRH mRNA and GnRH-R mRNA were reflected in the decrease of LH secretion. Blockade of micro opioid receptors affected neither GnRH mRNA and GnRH-R mRNA nor LH levels secretion. These results indicate that beta-endorphin displays a suppressive effect on the expression of the GnRH gene in the hypothalamus and GnRH-R gene in the anterior pituitary gland, but affects GnRH-R gene expression in a specific manner in the various parts of hypothalamus; altogether these events lead to the decrease in GnRH/LH secretion.

Melanocortin 4 receptor is not required for estrogenic regulations on energy homeostasis and reproduction

“…Such observations suggest a model that estrogens act on ERα expressed by POMC neurons to increase secretion of β-endorphin, which in return act through GnRH neurons to regulation HPG axis. This model is further supported by evidence that central infusion of β-endorphin strongly suppress hypothalamic GnRH gene expression [47] and secretion [48]. Of note, electron microscopic evidence also showed that β-endorphin-immunoreactive terminals directly synapse on the GnRH neurons soma in MPOA region [49].…”

Role of GnRH Neurons and Their Neuronal Afferents as Key Integrators between Food Intake Regulatory Signals and the Control of Reproduction

“…Several analyses revealed that β -Endorphin inhibits basal GnRH/gonadotropin secretion in different species and physiological conditions [71–75], as well as the electrical activity of a subpopulation of murine GnRH neurons [65]. Also, central injection of β -Endorphin is able to block the preovulatory surge of LH [76] and to inhibit sexual behaviour [77].…”

The Central Effect of β‐Endorphin and Naloxone on The Biosynthesis of GnRH and GnRH Receptor (GnRHR) in The Hypothalamic‐Pituitary Unit of Follicular‐Phase Ewes

“…Similarly, suppressive effects of β ‐endorphin on GnRH mRNA expression in the POA, AH and VM were observed in follicular‐phase ewes (Ciechanowska et al. ), suggesting that at least in part, a direct relationship exists between GnRH mRNA expression and GnRH biosynthesis. As GnRH mRNA in the SME was not detected in follicular‐phase ewes (Ciechanowska et al.…”

“…As GnRH mRNA in the SME was not detected in follicular‐phase ewes (Ciechanowska et al. ), it is reasonable to suggest that the post‐translational product of hormone gene in this structure results undoubtedly from GnRH axonal transport. The suppressive effect of β ‐endorphin on GnRH biosynthesis was also confirmed in this part of our current analyses when blockade of μ ‐opioid receptors with naloxone significantly increased GnRH concentration in the hypothalamus.…”

“…Our previous study on the functional interconnection between β ‐endorphinergic system and molecular processes governing the secretion of GnRH in sheep showed that β ‐endorphin significantly decreased GnRH mRNA level in the hypothalamus (Ciechanowska et al. ) and led to complex changes in the translational activity of the hypothalamic/anterior pituitary GnRHR. Due to lack of information about primary transcript degradation as well as post‐transcriptional modifications of mRNA(s) encoding GnRH and GnRHR, it was impossible to define a relationship between transcriptional activity and translational intensity of both these genes.…”