Neuropeptides in the gonads: from evolution to pharmacology

Abstract

Vertebrate gonads are the sites of synthesis and binding of many peptides that were initially classified as neuropeptides. These gonadal neuropeptide systems are neither well understood in isolation, nor in their interactions with other neuropeptide systems. Further, our knowledge of the control of these gonadal neuropeptides by peripheral hormones that bind to the gonads, and which themselves are under regulation by true neuropeptide systems from the hypothalamus, is relatively meager. This review discusses the existence of a variety of neuropeptides and their receptors which have been discovered in vertebrate gonads, and the possible way in which such systems could have evolved. We then focus on two key neuropeptides for regulation of the hypothalamo-pituitary-gonadal axis: gonadotropin-releasing hormone (GnRH) and gonadotropin-inhibitory hormone (GnIH). Comparative studies have provided us with a degree of understanding as to how a gonadal GnRH system might have evolved, and they have been responsible for the discovery of GnIH and its gonadal counterpart. We attempt to highlight what is known about these two key gonadal neuropeptides, how their actions differ from their hypothalamic counterparts, and how we might learn from comparative studies of them and other gonadal neuropeptides in terms of pharmacology, reproductive physiology and evolutionary biology.

Analysis of the expression of neurokinin B, kisspeptin, and their cognate receptors NK3R and KISS1R in the human female genital tract

“…These data suggest that peripheral reproductive tissues are a primary site of NKB expression and argue for an evolutionary conserved role of tachykinins in the regulation of reproduction acting locally at the level of the gonads. This appears to be the case for many other neuropeptide systems as well, which are synthesized in peripheral reproductive organs (36,38), where they might be involved in rapid local responses, modulate the peripheral effects of pituitary gonadotropins, or participate in the cross-talk with their brain counterparts. Admittedly however, the physiologic relevance of such local expression and actions remains undefined and needs additional investigation (38).…”

The Impact of Exposure to a Novel Female on Symptoms of Infection and on the Reproductive Axis

“…The significance of the testicular GnRH response is not entirely clear, since the effects of GnRH at this level are not yet fully understood and both inhibitory and stimulatory effects have been found [51]. Little is known about general actions of gonadal GnRH in birds, with one experiment demonstrating that in isolated granulosa cells from chicken (Gallus domesticus) , GnRH induces an increase in LH-stimulated progesterone production [56].…”

“…Additionally, because these neuropeptides are now known to be produced in the testes [51], we investigated any effect of treatment in the local regulation of their expression. To obtain a measure of proinflammatory responses, we quantified IL-1β in the brain.…”

Effects of Melatonin on Peripheral Reproductive Function: Regulation of Testicular GnIH and Testosterone

“…In a broader context, mammals also express the mammalian form of GnIH, RF-amide related peptide, and its receptors GPR74/GPR147/RFRPR in their gonads (46,47) Photoperiodic mammals have detectable levels of melatonin in their plasma and seminal plasma that are consistent with pineal secretions (48,49); they express melatonin subtype 1a receptor (21) in the testes and respond to melatonin challenge with reduced testosterone output from the testes (20 -22). Thus the testes of mammals are capable of directly responding to melatonin, and this effect may be mediated through the gonadal GnIH system as well.…”