Neuropeptides in the gonads: from evolution to pharmacology

Nicolette Mcguire

doi:10.3389/fphar.2010.00114

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.

Highlights

“What’s in a name? That which we call a rose By any other name would smell as sweet.” Romeo and Juliet (Act 2, scene 2)
Comparing the actions of hypothalamic and gonadal gonadotropin-inhibitory hormone (GnIH): What can we infer? the expression sites/pattern of GnIH and its receptor are suggestive of a role in steroid synthesis and gamete maturation, a general inhibitory action for the peptide cannot be inferred based on direct inhibition of gonadotropin-releasing hormone (GnRH) (Ducret et al, 2009) and luteinizing hormone (LH)/ follicle stimulating hormone (FSH) (Tsutsui et al, 2000) by its more characterized counterpart in the hypothalamus
Gonadal GnIH and the organism’s environment Is the gonadal GnIH system able to directly respond to environmental cues? New evidence from starling testes and ovaries indicates that LH/FSH-stimulated testosterone and estradiol levels are directly reduced by cortisol and melatonin (McGuire et al, 2010, unpublished observation)

Summary

Introduction

“What’s in a name? That which we call a rose By any other name would smell as sweet.” Romeo and Juliet (Act 2, scene 2). The conservation of localized gonadal regulation by gonadal neuropeptides across vertebrates has important implications for understanding the evolution, reproductive physiology and ecology of animals, along with the study and practice of reproductive health and medicine, both clinical and veterinary. Neuropeptides in the gonads Many neuronally produced hormones with important endocrine, behavioral, sensory and autonomic roles in the vertebrate brain are expressed by and may act directly within the gonads (Table 1; neuropeptide Y (NPY), Achi et al, 1995; bradykinin, Singh et al, 2007; corticotropin releasing factor (CRF), Huang et al, 1995; gonadotropin-releasing hormone (GnRH), Jones and Hsueh, 1981; Bahk et al, 1995; Pati and Habibi, 1998; gonadotropin-inhibitory hormone (GnIH), Hinuma et al, 2000; Bentley et al, 2008; kisspeptin, Castellano et al, 2006). It is somewhat logical to assume that the brain is able to interpret environmental and physiological cues and regulate its own steroid production, it is harder to understand www.frontiersin.org

Amphibians Reptiles

Rodent RFRP