Variation in Hypothalamic GnIH Expression and Its Association with GnRH and Kiss1 during Pubertal Progression in Male Rhesus Monkeys (Macaca mulatta)

Abstract

Modulation of pulsatile gonadotropin-releasing hormone (GnRH) secretion across postnatal development in higher primates is not fully understood. While gonadotropin-inhibitory hormone (GnIH) is reported to suppress reproductive axis activity in birds and rodents, little is known about the developmental trajectory of GnIH expression in rhesus monkeys throughout the pubertal transition. This study was aimed at examining the variation in GnIH immunoreactivity (-ir) and associated changes among GnIH, GnRH, and Kiss1 mRNA expression in the hypothalamus of infant, juvenile, prepubertal, and adult male rhesus monkeys. The brains from rhesus macaques were collected from infancy until adulthood and were examined using immunofluorescence and RT-qPCR. The mean GnIH-ir was found to be significantly higher in prepubertal animals (p < 0.01) compared to infants, and significantly reduced in adults (p < 0.001). Significantly higher (p < 0.001) GnRH and Kiss1 mRNA expression was noted in adults while GnIH mRNA expression was the highest at the prepubertal stage (p < 0.001). Significant negative correlations were seen between GnIH-GnRH (p < 0.01) and GnIH-Kiss1 (p < 0.001) expression. Our findings suggest a role for GnIH in the prepubertal suppression of the reproductive axis, with disinhibition of the adult reproductive axis occurring through decreases in GnIH. This pattern of expression suggests that GnIH may be a viable target for the development of novel therapeutics and contraceptives for humans.

The Thyroid Hormone Axis and Female Reproduction

“…Recent discoveries have suggested that the kisspeptin-GnRH axis may not be the only means of integrating peripheral environmental signals into the human reproductive axis. GnIH, also known as RFRP-3 in humans, is now also believed to mediate stress and metabolic signals in the control of GnRH, kisspeptin, and gonadotropin release in a variety of mammals [ 81 , 82 , 83 , 84 , 85 , 86 ]. Recent evidence suggests that THs could mediate this pathway ( Figure 2 ).…”