Endocrine Abstracts

JOINT1336

Neurons expressing growth hormone-releasing hormone (GHRH) are found in the arcuate nucleus of the hypothalamus (ARH), and they play a key role in stimulating GH secretion. Conversely, neurons expressing gonadotropin-releasing hormone (GnRH) and kisspeptins are stimulators of the luteinizing hormone (LH) secretion. Previous studies have shown that a subpopulation of GHRH neurons co-expresses kisspeptins in adult female mice but not in adult males or prepubertal animals. Thus, whether GHRH neurons can influence other endocrine axes beyond the somatotropic axis is unclear. The objective of this study was to evaluate whether the chemogenetic activation of GHRH neurons is able to modulate LH secretion in addition to GH. Initially, mice that constitutively express the cholinergic muscarinic receptor type 3 (hM3Dq) in GHRH neurons were produced. These animals were generated by crossing GHRH-Cre mice with a Cre-dependent hM3Dq-expressing strain. For acute stimulation of GHRH neurons, mice received an intraperitoneal injection of clozapine N-oxide (CNO) or vehicle solution (as control). Serial blood samples were collected before and after injection for subsequent hormonal dosage by ultra-sensitive enzyme-linked immunosorbent assay. Our findings indicate that the activation of GHRH neurons led to a robust GH secretion. Remarkably, a statistically significant increase in LH secretion was also observed in both male and female mice, either in adult (2-3 months) or prepubertal (~21 days of life) animals. Subsequently, GHRH-Cre and Kiss1-Cre adult mice received a bilateral injection in the ARH of an adeno-associated virus, inducing the expression of hM3Dq in Cre-positive cells. The chemogenic activation of either GHRH- or Kiss1-expressing cells also increased GH and LH circulating levels. Our findings indicate a crosstalk between the somatotropic and reproductive axis via ARH neuroendocrine neurons.