Pregnancy, but not dietary octanoic acid supplementation, stimulates the ghrelin-pituitary growth hormone axis in mice

Abstract

Circulating growth hormone (GH) concentrations increase during pregnancy in mice and remain pituitary-derived. Whether abundance or activation of the GH secretagogue ghrelin increase during pregnancy, or in response to dietary octanoic acid supplementation, is unclear. We therefore measured circulating GH profiles in late pregnant C57BL/6J mice and in aged-matched non-pregnant females fed with standard laboratory chow supplemented with 5% octanoic or palmitic (control) acid (n = 4–13/group). Serum total and acyl-ghrelin concentrations, stomach and placenta ghrelin mRNA and protein expression, Pcsk1 (encoding prohormone convertase 1/3) and Mboat4 (membrane bound O-acyl transferase 4) mRNA were determined at zeitgeber (ZT) 13 and ZT23. Total and basal GH secretion were higher in late pregnant than non-pregnant mice (P < 0.001), regardless of diet. At ZT13, serum concentrations of total ghrelin (P = 0.004), but not acyl-ghrelin, and the density of ghrelin-positive cells in the gastric antrum (P = 0.019) were higher, and gastric Mboat4 and Pcsk1 mRNA expression were lower in pregnant than non-pregnant mice at ZT23. In the placenta, ghrelin protein was localised mostly to labyrinthine trophoblast cells. Serum acyl-, but not total, ghrelin was lower at mid-pregnancy than in non-pregnant mice, but not different at early or late pregnancy. In conclusion, dietary supplementation with 5% octanoic acid did not increase activation of ghrelin in female mice. Our results further suggest that increases in maternal GH secretion throughout murine pregnancy are not due to circulating acyl-ghrelin acting at the pituitary. Nevertheless, time-dependent increased circulating total ghrelin could potentially increase ghrelin action in tissues that express the acylating enzyme and receptor.

Ghrelin promotes angiogenesis by activating the Jagged1/Notch2/VEGF pathway in preeclampsia

“…12 As mentioned above, abnormal angiogenesis and hypertension are the typical performance of PE, so we suspected that ghrelin may be related to PE. Previous study showed that ghrelin protein can be detected in trophoblast cells, 13 indicating that ghrelin may play an important physiological role in healthy pregnancy. Ghrelin levels increase in the first trimester, reach a peak in the second trimester, and drop to their lowest in the third trimester.…”

The Role of the Gastric Hormones Ghrelin and Nesfatin-1 in Reproduction

“…Its mRNA is detectable on embryonic day 12 and 17 [16], with a peak at day 16 and a decrease thereafter [40]. In detail, ghrelin is mainly expressed in the cytoplasm of labyrinth trophoblasts in rat placenta [40] as well as in the placenta of mice [41]. Noteworthy, under conditions of intra-uterine growth restriction in rats, placental ghrelin mRNA and peptide were elevated [42].…”

“…In rodents, at mid-pregnancy, such as on day 10 and 15 of pregnancy, plasma ghrelin was decreased [12,41], while on day 20 [12] and day 23 [41] it was increased compared to non-pregnant rats [12]. Comparison of fasting plasma ghrelin concentrations throughout pregnancy showed a decrease with time, resulting in the lowest ghrelin level by day 18 of pregnancy in one study [73], while in nonfasted rats an increase of circulating ghrelin throughout pregnancy was observed [13]; in both investigations there was a normalization of ghrelin concentration at parturition [73].…”

Maternal adaptations to food intake across pregnancy: Central and peripheral mechanisms

“…The role of maternal gut hormones in GI adaptations to normal pregnancy is underinvestigated, and few studies have explored the capacity of these hormones to alter GI mucosal structure and affect satiety (55, 56). Current evidence on plasma acyl‐ghrelin (the active form of ghrelin) concentrations during pregnancy is equivocal, with reports of an increase (57) or decrease (58) in women, an increase in rats (59), and a decrease in mice (60). Furthermore, the effects of ghrelin on food intake during pregnancy are mostly unknown.…”

“…GH levels increase throughout human pregnancy, with pituitary‐derived GH predominant in early pregnancy, whereas the placental GH variant predominates from mid to late pregnancy (Figure 3, (93)). Rats and mice do not possess the placental variant, and instead, pituitary‐derived GH levels increase during pregnancy, likely in response to placental signals (60, 94). Systemic infusion of human placental GH into pregnant mice reduced maternal insulin sensitivity without affecting food intake or body weight (95).…”