Growth hormone receptor in dopaminergic neurones regulates stress‐induced prolactin release in male mice. (26th March 2021)

• Record Type: Journal Article
• Authors: Wasinski, Frederick; Chaves, Fernanda M.; Pedroso, João A. B.; Mansano, Naira S.; Camporez, João Paulo; Gusmão, Daniela O.; List, Edward O.; Kopchick, John J.; Frazão, Renata; Szawka, Raphael E.; Donato, Jose
• Is Part Of: Journal of neuroendocrinology. Volume 33:Number 3(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-03-26
• Subjects: dopamine transporter -- hypothalamus -- pituitary -- tuberoinfundibular dopaminergic -- tyrosine hydroxylase; Neuroendocrinology -- Periodicals; 616.4
• DOI: 10.1111/jne.12957
• Languages: English
• ISSNs: 0953-8194

Abstract

Abstract: Arcuate nucleus (ARH) dopaminergic neurones regulate several biological functions, including prolactin secretion and metabolism. These cells are responsive to growth hormone (GH), although it is still unknown whether GH action on ARH dopaminergic neurones is required to regulate different physiological aspects. Mice carrying specific deletion of GH receptor (GHR) in tyrosine hydroxylase (TH)‐ or dopamine transporter (DAT)‐expressing cells were produced. We investigated possible changes in energy balance, glucose homeostasis, fertility, pup survival and restraint stress‐induced prolactin release. GHR deletion in DAT‐ or TH‐expressing cells did not cause changes in food intake, energy expenditure, ambulatory activity, nutrient oxidation, glucose tolerance, insulin sensitivity and counter‐regulatory response to hypoglycaemia in male and female mice. In addition, GHR deletion in dopaminergic cells caused no gross effects on reproduction and pup survival. However, restraint stress‐induced prolactin release was significantly impaired in DAT‐ and TH‐specific GHR knockout male mice, as well as in pegvisomant‐treated wild‐type males, whereas an intact response was observed in females. Patch clamp recordings were performed in ARH DAT neurones and, in contrast to prolactin, GH did not cause acute changes in the electrical activity of DAT neurones. Furthermore, TH phosphorylation at Ser 40 in ARH neurones and median eminence axonal terminals was not altered in DAT‐specific GHR knockout male mice during restraint stress. In conclusion, GH action in dopaminergic neurones is required for stress‐induced prolactin release in male mice, suggesting the existence of sex differences in the capacity of GHR signalling to affect prolactin secretion. The mechanism behind this regulation still needs to be identified. Abstract : Recent studies have investigated possible physiological roles played by growth hormone (GH) action on specific hypothalamic neurones. Tuberoinfundibular dopaminergic (TIDA) neurones exhibit signal transducer and activator of transcription 5 phosphorylation after an acute GH injection, suggesting that these cells present functional GH receptor (GHR). TIDA neurones control pituitary prolactin secretion and metabolism. However, it is unknown whether GH action on TIDA neurones regulates those physiological functions. To investigate the importance of GHR signalling in TIDA neurones, we produced two cell‐specific knockout mice by ablating GHR either in tyrosine hydroxylase (TH‐) or dopamine transporter (DAT)‐expressing cells. We determined possible changes in energy balance, glucose homeostasis, fertility, pup survival and restraint stress‐induced prolactin release. GHR deletion in DAT‐ or TH‐expressing cells did not cause changes in food intake, energy expenditure, ambulatory activity, nutrient oxidation, glucose tolerance, insulin sensitivity and counter‐regulatory response to hypoglycaemia in male and female mice. In addition, GHR deletion in dopaminergic cells caused no major effects on reproduction and pup survival. However, restraint stress‐induced prolactin release was significantly impaired in DAT‐ and TH‐specific GHR knockout male mice, whereas an intact response was observed in mutant females. Patch clamp recordings were performed in ARH DAT neurones and, in contrast to prolactin, GH did not cause acute changes in the electrical activity of DAT neurones. Furthermore, TH phosphorylation at Ser40 in ARH neurones and median eminence during restraint stress was not altered in DAT‐specific GHR knockout male mice. In conclusion, GH action in dopaminergic neurones is required for stress‐induced prolactin release in male mice. Because prolactin has anxiolytic and anti‐stress effects, the cross‐talk between GH and prolactin is possibly related to fine adjustments in the perception and response to stressful stimuli.