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Corticotropin-releasing hormone (CRH) cells are the dominant neuronal population responsive to the growth hormone (GH) in the paraventricular nucleus of the hypothalamus (PVH). However, the physiological importance of GH receptor (GHR) signaling in CRH neurons is currently unknown. Thus, the main objective of the present study was to investigate the consequences of GHR ablation in CRH-expressing cells of male and female mice. GHR ablation in CRH cells did not cause significant changes in body weight, body composition, food intake, substrate oxidation, locomotor activity, glucose tolerance, insulin sensitivity, counterregulatory response to 2-deoxy-D-glucose and ghrelin-induced food intake. However, reduced energy expenditure was observed in female mice carrying GHR ablation in CRH cells. The absence of GHR in CRH cells did not affect anxiety, circadian glucocorticoid levels or restraint-stress-induced corticosterone secretion and activation of PVH neurons in both male and female mice. In summary, GHR ablation, specifically in CRH-expressing neurons, does not lead to major alterations in metabolism, hypothalamic-pituitary-adrenal axis, acute stress response or anxiety in mice. Considering the previous studies showing that central GHR signaling regulates homeostasis in situations of metabolic stress, future studies are still necessary to identify the potential physiological importance of GH action on CRH neurons.

Classical studies suggest that growth hormone (GH) secretion is controlled by negative-feedback loops mediated by GH-releasing hormone (GHRH)- or somatostatin-expressing neurons. Catecholamines are known to alter GH secretion and neurons expressing TH are located in several brain areas containing GH-responsive cells. However, whether TH-expressing neurons are required to regulate GH secretion via negative-feedback mechanisms is unknown. In the present study, we showed that between 50% and 90% of TH-expressing neurons in the periventricular, paraventricular, and arcuate hypothalamic nuclei and locus ceruleus of mice exhibited STAT5 phosphorylation (pSTAT5) after an acute GH injection. Ablation of GH receptor (GHR) from TH cells or in the entire brain markedly increased GH pulse secretion and body growth in both male and female mice. In contrast, GHR ablation in cells that express the dopamine transporter (DAT) or dopamine β-hydroxylase (DBH; marker of noradrenergic/adrenergic cells) did not affect body growth. Nevertheless, less than 50% of TH-expressing neurons in the hypothalamus were found to express DAT. Ablation of GHR in TH cells increased the hypothalamic expression of Ghrh mRNA, although very few GHRH neurons were found to coexpress TH- and GH-induced pSTAT5. In summary, TH neurons that do not express DAT or DBH are required for the autoregulation of GH secretion via a negative-feedback loop. Our findings revealed a critical and previously unidentified group of catecholaminergic interneurons that are apt to sense changes in GH levels and regulate the somatotropic axis in mice. SIGNIFICANCE STATEMENT Textbooks indicate until now that the pulsatile pattern of growth hormone (GH) secretion is primarily controlled by GH-releasing hormone and somatostatin neurons. The regulation of GH secretion relies on the ability of these cells to sense changes in circulating GH levels to adjust pituitary GH secretion within a narrow physiological range. However, our study identifies a specific population of tyrosine hydroxylase-expressing neurons that is critical to autoregulate GH secretion via a negative-feedback loop. The lack of this mechanism in transgenic mice results in aberrant GH secretion and body growth. Since GH plays a key role in cell proliferation, body growth, and metabolism, our findings provide a major advance to understand how the brain regulates the somatotropic axis., (Copyright © 2020 the authors.)

Neurones expressing the melanin-concentrating hormone (MCH) can be found in the medial preoptic area (mPOA) and ventral aspects of the periventricular preoptic nucleus of rats by mid-to-late lactation and this expression disappears after weaning. The transitory expression of MCH in the preoptic area suggests a role for these neurones in the control of the end of lactation. However, the neurochemical identity of mPOA MCH neurones and the regulatory factors that control the transient MCH expression remain largely unknown, especially in the mouse. In the present study, we showed that mice also present the transitory expression of MCH in the mPOA at late lactation. mPOA MCH cells did not colocalise significantly with markers of GABAergic (VGAT), glutamatergic (VGLUT2 and VGLUT3) or dopaminergic (tyrosine hydroxylase) neurones. mPOA MCH cells also did not express Kiss1 or oxytocin. By contrast, approximately 70% and 90% of mPOA MCH neurones colocalised with oestrogen receptor α and prolactin-induced phosphorylated signal transducer and activator of transcription 5 (STAT5), respectively. Finally, we demonstrated that the number of MCH neurones in the mPOA is significantly higher in females during the first lactation, compared to mice on the second lactation or pregnant mice during the first lactation or brain-specific STAT5 knockout mice during the first lactation. In summary, our findings indicate that MCH neurones in the mPOA of lactating mice are sensitive to oestrogens and prolactin. Thus, mPOA MCH expression is possibly influenced by hormonal variations. Furthermore, the STAT5 signalling pathway is likely involved in the regulation of MCH expression in the mPOA of lactating mice., (© 2019 British Society for Neuroendocrinology.)

Several hypothalamic neuronal populations are directly responsive to growth hormone (GH) and central GH action regulates glucose and energy homeostasis. However, the potential role of GH signaling in proopiomelanocortin (POMC) neurons has not been studied yet. Thus, we investigated whether POMC neurons are responsive to GH and if ablation of GH receptor (GHR) or STAT5 in POMC cells leads to metabolic imbalances. Approximately 60% of POMC neurons of the arcuate nucleus exhibited STAT5 phosphorylation after intracerebroventricular GH injection. Ablation of GHR or STAT5 in POMC cells did not affect energy or glucose homeostasis. However, glucoprivic hyperphagia was blunted in male and female GHR knockout mice, and in male POMC-specific STAT5 knockout mice. Additionally, the absence of GHR in POMC neurons decreased glycemia during prolonged food restriction in male mice. Thus, GH action in POMC neurons regulates glucoprivic hyperphagia as well as blood glucose levels during prolonged food restriction., (Copyright © 2019 Elsevier B.V. All rights reserved.)