Effects of melanocortins on fetal development

Abstract

Melanocortins, adrenocorticotropic hormone (ACTH) and α-, β-, and γ-melanocyte-stimulating hormone (MSH) are produced in the placenta and secreted into embryos/fetuses. ACTH concentrations are higher in fetal plasma than in maternal plasma and peak at mid-gestation in rats, whereas ACTH production starts in the anterior lobe of the fetal pituitary at later stages. Melanocortin receptors (MC1-5R), receptors for ACTH and α-, β- and γ-MSH, are expressed in various adult organs. The specific function of these receptors has been well examined in the hypothalamic-pituitary-adrenocortical (HPA) axis and the HPA axis-like network in the skin, and anti-inflammatory effects for white blood cells have also been investigated. MC2R and/or MC5R are also expressed in the testis, lung, kidney, adrenal, liver, pancreas, brain and blood cells at different stages in mouse and rat embryos/fetuses. Melanocortins in embryos and fetuses promote maturation of the HPA axis and also contribute to the development of lung, testis, brain and blood cells. Recently, a unique ACTH function was revealed in fetuses: placental ACTH, which is secreted by the maternal leukemia inhibitory factor (LIF), and induces LIF secretion from fetal nucleated red blood cells. Finally, the maternal LIF-placental ACTH-fetal LIF signal relay regulates the LIF level and promotes neurogenesis in fetuses, which suggests that ACTH acts as a signal transducer or effector for fetal development in the maternal-fetal signal pathway.

The Suppression of Maternal–Fetal Leukemia Inhibitory Factor Signal Relay Pathway by Maternal Immune Activation Impairs Brain Development in Mice

“…We have previously shown that one of the pro-inflammatory cytokine belonging to the IL-6 family cytokines, leukemia inhibitory factor (LIF), is required for fetal brain development [ 11 , 12 ]. We also demonstrated that rat maternal LIF induces adrenocorticotropic hormone (ACTH) from the placenta, which in turn stimulates fetal nucleated red blood cells to secrete LIF, leading finally to neurogenesis in the cerebrum of the fetus [ 13 , 14 ]. This maternal—fetal signal relay pathway of maternal LIF–ACTH–fetal LIF via the placenta (maternal–fetal LIF signal relay) was shown in rats at mid-gestational stage [ 14 ].…”

Maternal and fetal outcome in Swedish women with erythropoietic protoporphyria

“…An increase in melanocyte‐stimulating hormone (α‐MSH) produced by the placenta is one of many physiological and hormonal changes in pregnancy and may have a mechanistic role in ameliorating EPP symptoms. Of note, synthetic α‐MSH is an emerging treatment to increase tolerance to sunlight in EPP …”

The Role of Gp91phox NADPH Oxidase during the Gestational Period of Mice

“…It is well documented that ACTH is important for embryonic differentiation [6]. In the placentas, MC2R (ACTH-R) is known to be high, and a fetal animal is directly affected by ACTH level [7].…”