The Pregnancy‐Induced Increase in Baseline Circulating Growth Hormone in Rats is not Induced by Ghrelin

Abstract

The elevation in baseline circulating growth hormone (GH) that occurs in pregnant rats is thought to arise from increased pituitary GH secretion, but the underlying mechanism remains unclear. Distribution, Fourier and algorithmic analyses confirmed that the pregnancy-induced increase in circulating GH in 3-week pregnant rats was due to a 13-fold increase in baseline circulating GH (P < 0.01), without any significant alteration in the parameters of episodic secretion. Electron microscopy revealed that pregnancy resulted in a reduction in the proportion of mammosomatotrophs (P < 0.01) and an increase in type II lactotrophs (P < 0.05), without any significant change in the somatotroph population. However, the density of the secretory granules in somatotrophs from 3-week pregnant rats was reduced (P < 0.05), and their distribution markedly polarised; the granules being grouped nearest the vasculature. Pituitary GH content was not increased, but steady-state GH mRNA levels declined progressively during pregnancy (P < 0.05). In situ hybridisation revealed that pregnancy was accompanied by a suppression of GH-releasing hormone mRNA expression in the arcuate nuclei (P < 0.05) and enhanced somatostatin mRNA expression in the periventricular nuclei (P < 0.05), an expression pattern normally associated with increased GH feedback. Although gastric ghrelin mRNA expression was elevated by 50% in 3-week pregnant rats (P < 0.01), circulating ghrelin, GH-secretagogue receptor mRNA expression and the GH response to a bolus i.v. injection of exogenous ghrelin were all largely unaffected during pregnancy. Although trace amounts of 'pituitary' GH could be detected in the placenta with radioimmunoassay, significant GH-immunoreactivity could not be observed by immunohistochemistry, indicating that rat placenta itself does not produce 'pituitary' GH. Although not excluding the possibility that the pregnancy-associated elevation in baseline circulating GH could arise from alternative extra-pituitary sources (e.g. the ovary), our data indicate that this phenomenon is most likely to result from a direct alteration of somatotroph function.

Maternal Mineral and Bone Metabolism During Pregnancy, Lactation, and Post-Weaning Recovery

“…Estradiol, estriol, estrone, progesterone, prolactin, placental lactogen, and placental growth hormone each increases significantly (232,268,852,979). Conversely, IGF-I decreases during late pregnancy in rats, consistent with a suppression in pituitary growth hormone (268,645). Oxytocin increases fivefold during pregnancy in rats and reaches its highest levels during parturition (1010).…”

Fetus-derived DLK1 is required for maternal metabolic adaptations to pregnancy and is associated with fetal growth restriction

“…GH levels are elevated in pregnancy in both humans and rodents (although the source of rodent GH in pregnancy is not clear[23], as they lack the placental GH gene variant found in primates[24]). Since GH-like molecules promote maternal adaptations to pregnancy[24], we asked if circulating GH was affected by Dlk1 during gestation.…”

Rising maternal circulating GH during murine pregnancy suggests placental regulation

“…These prolactin-related peptides are, however, unlikely to have the same effects as GH, since in mouse prolactin and GH bind poorly to each other’s receptors (9). Amongst species lacking placental GH, GH profiles during pregnancy have only been reported in rats (10). In this species, GH remains pulsatile throughout pregnancy, with relatively unchanged pulsatile secretion superimposed on progressively increasing basal secretion (10).…”

“…Amongst species lacking placental GH, GH profiles during pregnancy have only been reported in rats (10). In this species, GH remains pulsatile throughout pregnancy, with relatively unchanged pulsatile secretion superimposed on progressively increasing basal secretion (10). In the pregnant mouse, GH measured in single samples increases 30- to 50-fold near term (11), but the patterns of circulating GH during pregnancy have not been reported.…”