Neurochemical phenotype of growth hormone‐responsive cells in the mouse paraventricular nucleus of the hypothalamus

Abstract

Multiple neuroendocrine, autonomic and behavioral responses are regulated by the paraventricular nucleus of the hypothalamus (PVH). Previous studies have shown that PVH neurons express the growth hormone (GH) receptor (GHR), although the role of GH signaling on PVH neurons is still unknown. Given the great heterogeneity of cell types located in the PVH, we performed a detailed analysis of the neurochemical identity of GH‐responsive cells to understand the possible physiological importance of GH action on PVH neurons. GH‐responsive cells were detected via the phosphorylated form of the signal transducer and activator of transcription‐5 (pSTAT5) in adult male mice that received an intraperitoneal GH injection. Approximately 51% of GH‐responsive cells in the PVH co‐localized with the vesicular glutamate transporter 2. Rare co‐localizations between pSTAT5 and vesicular GABA transporter or vasopressin were observed, whereas approximately 20% and 38% of oxytocin and tyrosine hydroxylase (TH) cells, respectively, were responsive to GH in the PVH. Approximately 55%, 35% and 63% of somatostatin, thyrotropin‐releasing hormone (TRH) and corticotropin‐releasing hormone (CRH) neurons expressed GH‐induced pSTAT5, respectively. Additionally, 8%, 49% and 75% of neuroendocrine TH, TRH and CRH neurons, and 67%, 32% and 74% of nonneuroendocrine TH, TRH and CRH neurons were responsive to GH in the PVH of Fluoro‐Gold‐injected mice. Our findings suggest that GH action on PVH neurons is involved in the regulation of the thyroid, somatotropic and adrenal endocrine axes, possibly influencing homeostatic and stress responses.

Growth hormone receptor in dopaminergic neurones regulates stress‐induced prolactin release in male mice

“…Thus, acute changes in GHR signalling in dopaminergic neurones may be necessary to fully induce prolactin secretion during restraint stress. Of note, although our study focused on investigating ARH dopaminergic neurones as putative mediators of GH action to regulate prolactin secretion, different hypothalamic and brainstem areas contain TH‐expressing neurones that are responsive to GH, including the periventricular nucleus, paraventricular nucleus of the hypothalamus and locus coeruleus 19,42 . Additionally, we cannot rule out the participation of catecholaminergic cells of the periphery.…”

“…Growth hormone‐responsive neurones were identified in the present study via the expression of pSTAT5 in mice previously injected with GH. Although this method has been extensively used by our research group, 13,15‐19,29‐31,40‐43 we cannot guarantee that all pSTAT5 positive cells express GHR. Indeed, no study so far has demonstrated that TIDA neurones express Ghr mRNA.…”

Central Regulation of Metabolism by Growth Hormone

“…The importance of GHR signaling in several newly described populations of GH-responsive neurons remains undetermined [ 36 , 37 ]. Recently, our research group identified the neurochemical phenotype of GH-responsive cells in mouse PVH [ 104 ]. The PVH contains several neurochemically defined neuronal populations [ 105 ], so the identification of those that are responsive to GH allows understanding the possible physiological importance of GHR signaling in this hypothalamic nucleus.…”

“…The PVH contains several neurochemically defined neuronal populations [ 105 ], so the identification of those that are responsive to GH allows understanding the possible physiological importance of GHR signaling in this hypothalamic nucleus. We found that 38%, 55%, 35% and 63% of TH, SST, thyrotropin-releasing hormone (TRH) and corticotropin-releasing hormone (CRH) neurons exhibited GH-induced pSTAT5, respectively [ 104 ] ( Figure 3 B). The majority of neuroendocrine SST, TRH and CRH neurons were responsive to GH, indicating that central GH signaling probably regulates somatotropic, thyroid and adrenal endocrine axes ( Figure 2 ).…”

“…The majority of neuroendocrine SST, TRH and CRH neurons were responsive to GH, indicating that central GH signaling probably regulates somatotropic, thyroid and adrenal endocrine axes ( Figure 2 ). However, non-neuroendocrine neurons were also responsive to GH in the PVH, including 67%, 32% and 74% of non-neuroendocrine TH, TRH and CRH PVH neurons, respectively [ 104 ]. This study gives an idea about the diversity of functions that central GHR signaling may regulate in one specific hypothalamic nucleus.…”