Growth hormone signaling in the brain as a mediator of puberty and fertility

Abstract

Growth hormone (GH) is an important factor involved in the regulation of multiple biological functions. However, although the influence of GH is widespread throughout several organs and tissues, the effects of GH on brain functions such as those related to reproductive functions are still elusive. GH deficiency or resistance can be related to late puberty onset, lack of sexual maturation and infertility. In contrast, GH therapy can accelerate puberty onset or be used to increase pregnancy rates in woman treating fertility related problems. Suggesting, that GH can modulate reproduction. However, the molecular and cellular mechanisms by which GH could potentially modulate the reproductive system are not fully understood. We present conclusive evidence demonstrating that GH has a direct effect on areas of interest in the nervous system, either by identifying the main pathway recruited after GH receptor activation (STAT5) or by demonstrating preliminary results showing that human GH can modulate ion channels to induce rapid effects on hypothalamic neurons resting membrane potential. Indicating that the brain is a potentially important GH-target tissue. Based on the preliminary results presented, our goal is to understand whether GH signaling in the brain is required to sexual maturation and maintenance of reproductive functions. For this purpose, we will use the Cre-LoxP technology to induce GH receptor deletion in specific neuronal populations (kiss1-Cre, leptin receptor-Cre) or globally in the brain (Nestin-Cre model). We will be able to identify whether there is a specific population in which this hormone can direct act to modulate the HPG axis. Moreover, using the whole-cell path-clamp recordings in brain slices, we will complement the investigation regarding the effects of exogenous GH (human and mouse) on the biophysical properties of different hypothalamic populations. The proposed research has the potential to contribute significantly to the literature, demonstrating whether GH acts as a signal in the hypothalamus to modulate events that culminate in sexual maturation and in the maintenance of reproductive functions. (AU)