Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil.
Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil.
Brain Res. 2019 Jul 1;1714:210-217. doi: 10.1016/j.brainres.2019.03.003. Epub 2019 Mar 6.
Growth hormone (GH) and prolactin (PRL) are known as pleiotropic hormones. Accordingly, the distribution of their receptors comprises several organs and tissues, including the central nervous system. The appropriate secretion of both hormones is essential for sexual maturation and maintenance of reproductive functions, while defects in their secretion affect puberty onset and can cause infertility. Conversely, GH therapy at a prepubertal age may accelerate puberty. On the other hand, hyperprolactinemia is a frequent cause of infertility. While the action of PRL in some central components of the Hypothalamic-Pituitary-Gonadal (HPG) axis, such as the kisspeptin neurons, has been well documented, the possible effects of GH in the hypothalamus are still elusive. Thus, the present study was designed to investigate whether somatomammotropin hormones are able to modulate the activity of critical neuronal components of the HPG axis, including kisspeptin neurons and cells of the ventral premammillary nucleus (PMv). Our results revealed that GH effects in kisspeptin neurons of the anteroventral periventricular and rostral periventricular nuclei or in PMv neurons relies predominantly on the recruitment of the signal transducer and activator of transcription 5 (STAT5) rather than through acute changes in resting membrane potential. Importantly, kisspeptin neurons located at the arcuate nucleus were not directly responsive to GH. Additionally, our findings further identified PMv neurons as potential targets of PRL, since PRL induces the phosphorylation of STAT5 and depolarizes PMv neurons. Combined, our data provide evidence that GH and PRL may affect the HPG axis via specific hypothalamic neurons.
生长激素（GH）和催乳素（PRL）被称为多效激素。因此，它们的受体分布包括多个器官和组织，包括中枢神经系统。这两种激素的适当分泌对性成熟和生殖功能的维持至关重要，而它们分泌的缺陷会影响青春期的开始，并可能导致不孕。相反，在青春期前使用 GH 治疗可能会加速青春期的到来。另一方面，高催乳素血症是不孕的常见原因。虽然催乳素在下丘脑-垂体-性腺（HPG）轴的一些中枢成分中的作用，如 kisspeptin 神经元，已经得到了很好的证明，但 GH 在下丘脑的可能作用仍然难以捉摸。因此，本研究旨在探讨生长激素是否能够调节 HPG 轴的关键神经元成分的活性，包括 kisspeptin 神经元和腹侧前乳突核（PMv）细胞。我们的结果表明，GH 对腹前室旁核和前室旁核的 kisspeptin 神经元或 PMv 神经元的作用主要依赖于信号转导和转录激活因子 5（STAT5）的募集，而不是通过静息膜电位的急性变化。重要的是，弓状核中的 kisspeptin 神经元对 GH 没有直接反应。此外，我们的研究结果还进一步确定了 PMv 神经元是 PRL 的潜在靶标，因为 PRL 诱导 STAT5 的磷酸化并使 PMv 神经元去极化。综上所述，我们的数据提供了证据，表明 GH 和 PRL 可能通过特定的下丘脑神经元影响 HPG 轴。
