Rising maternal circulating GH during murine pregnancy suggests placental regulation

Gatford, Kathryn L.; Mühlhäusler, Beverly S.; Huang, Lili; Sim, Pamela; Roberts, Claire T.; Velhuis, Johannes D; Chen, Chen

doi:10.1530/ec-17-0032

Cited by 22 publications

(38 citation statements)

References 44 publications

(63 reference statements)

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“…As with the PRLR, growth hormone receptor and growth hormone-induced pSTAT5 are observed in the PVN. 28 Growth hormone secretion is elevated during the second half of pregnancy in mice 25 and plays a key role in metabolic adaptations during pregnancy. 43 In early pregnancy, PVN pSTAT5 levels were low, and did not reflect changes in prolactin.…”

Section: Discussionmentioning

confidence: 99%

Prolactin receptor‐mediated activation of pSTAT5 in the pregnant mouse brain

Gustafson

Ladyman

McFadden

et al. 2020

J Neuroendocrinology

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Pregnancy represents a period of remarkable adaptive physiology throughout the body, with many of these important adaptations mediated by changes in gene transcription in the brain. A marked activation of the transcription factor signal transducer and activator of transcription 5 (STAT5) has been described in the brain during pregnancy and likely drives some of these changes. We aimed to investigate the physiological mechanism causing this increase in phosphorylated STAT5 (pSTAT5) during pregnancy. In various tissues, STAT5 is known to be activated by a number of different cytokines, including erythropoietin, growth hormone and prolactin. Because the lactogenic hormones that act through the prolactin receptor (PRLR), prolactin and its closely-related placental analogue placental lactogen, are significantly increased during pregnancy, we hypothesised that this receptor was primarily responsible for the pregnancy-induced increase in pSTAT5 in the brain. By examining temporal changes in plasma prolactin levels and the pattern of pSTAT5 immunoreactivity in the hypothalamus during early pregnancy, we found that the level of pSTAT5 was sensitive to circulating levels of endogenous prolactin. Using a transgenic model to conditionally delete PRLRs from forebrain neurones (Prlr lox/lox /CamK-Cre), we assessed the relative contribution of the PRLR to the up-regulation of pSTAT5 in the brain of pregnant mice. In the absence of PRLRs on most forebrain neurones, a significant reduction in pSTAT5 was observed throughout the hypothalamus and amygdala in late pregnancy, confirming that PRLR is key in mediating this response. The exception to this was the hypothalamic paraventricular nucleus, where only 17% of pSTAT5 immunoreactivity during pregnancy was in PRLR-expressing cells. Taken together, these data indicate that, although there are region-specific mechanisms involved, lactogenic activity through the PRLR is the primary signal activating STAT5 in the brain during pregnancy.

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Section: Discussionmentioning

confidence: 99%

Prolactin receptor‐mediated activation of pSTAT5 in the pregnant mouse brain

Gustafson

Ladyman

McFadden

et al. 2020

J Neuroendocrinology

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“…These adaptations are thought to be mediated by hormones secreted during pregnancy, principally prolactin and placental lactogens (59). High amounts of GH are also secreted during pregnancy in both humans and rodents (9). In a recent study, we showed that ablation of GHR in the entire brain or in LepR-expressing cells improved the systemic insulin sensitivity of pregnant mice (51).…”

Section: Gh Action In the Cns Regulates Metabolismmentioning

confidence: 99%

“…During fasting, neuropeptide Y (NPY)-expressing neurons become active (6), and NPY secretion is responsible for decreasing GH pulsatility via the activation of the Y1 receptor (5). In addition to fasting, other conditions that induce increased GH secretion include hypoglycemia (7), physical exercise (8) and pregnancy (9).…”

Section: Introductionmentioning

confidence: 99%

Effects of growth hormone in the central nervous system

Wasinski

Frazão

Donato

2019

Archives of Endocrinology and Metabolism

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Growth hormone (GH) is best known for its effect stimulating tissue and somatic growth through the regulation of cell division, regeneration and proliferation. However, GH-responsive neurons are spread over the entire central nervous system, suggesting that they have important roles in the brain. The objective of the present review is to summarize and discuss the potential physiological importance of GH action in the central nervous system. We provide evidence that GH signaling in the brain regulates the physiology of numerous functions such as cognition, behavior, neuroendocrine changes and metabolism. Data obtained from experimental animal models have shown that disruptions in GH signaling in specific neuronal populations can affect the reproductive axis and impair food intake during glucoprivic conditions, neuroendocrine adaptions during food restriction, and counter-regulatory responses to hypoglycemia, and they can modify gestational metabolic adaptions. Therefore, the brain is an important target tissue of GH, and changes in GH action in the central nervous system can explain some dysfunctions presented by individuals with excessive or deficient GH secretion. Furthermore, GH acts in specific neuronal populations during situations of metabolic stress to promote appropriate physiological adjustments that restore homeostasis. Arch

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“…17 By contrast, pituitary mGH production continues during pregnancy in the mouse, and its basal secretion increases from mid-pregnancy onward because the mouse placenta does not produce an equivalent to human PGH. 17…”

Section: Dupli C Ati On and The E Volutionary Succe Ss Of Pl Acentamentioning

confidence: 99%

Obesity and regulation of human placental lactogen production in pregnancy

Cattini

Jin

Jarmasz

et al. 2020

J Neuroendocrinology

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The four genes coding for placental members of the human (h) growth hormone (GH) family include two that code independently for placental lactogen (PL), also known as chorionic somatomammotrophin hormone, one that codes for placental growth hormone (PGH) and a pseudogene for which RNA but no protein product is reported. These genes are expressed preferentially in the villus syncytiotrophoblast of the placenta in pregnancy. In higher primates, the placental members, including hPL and PGH, are the result of multiple duplication events of the GH gene.

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Rising maternal circulating GH during murine pregnancy suggests placental regulation

Cited by 22 publications

References 44 publications

Prolactin receptor‐mediated activation of pSTAT5 in the pregnant mouse brain

Prolactin receptor‐mediated activation of pSTAT5 in the pregnant mouse brain

Effects of growth hormone in the central nervous system

Obesity and regulation of human placental lactogen production in pregnancy

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