Is α MSH a trophic hormone to adrenal function in the foetus?

Abstract

FUNCTIONAL development of the pituitary–adrenal axis in the foetus seems to be of considerable importance in influencing the maturation of other foetal organ systems, and the timing of parturition^1–2. In several species including man^3,4, sheep² and rabbits⁵, there is evidence for an increase in foetal adrenal function in late pregnancy, which seems to depend on the activities of the foetal pituitary and hypothalamus². The factors responsible for stimulating foetal adrenal development during late gestation remain poorly understood, however. From detailed studies in foetal sheep, it is apparent that the prepartum acceleration of adrenal growth and glucocorticoid secretion is not preceded by elevated ACTH concentrations in the foetal plasma^6,7. But, prostaglandin E₂ (PGE₂) administered intra-arterially into the foetus stimulated an increase in the concentration of cortisol in foetal plasma⁸ at a stage of pregnancy when the adrenal gland was essentially unresponsive to endogenous or exogenous ACTH (refs 2, 9). Experiments in newborn lambs suggest that the pituitary or brain rather than the foetal adrenal gland was the likely site of the PGE₂ action¹⁰, raising the possibility that other pituitary peptides might mediate this effect. The ACTH related peptides, α-melanocyte stimulating hormone (αMSH) and corticotropin-like intermediate lobe peptide (CLIP) have been identified in human foetal pituitaries, and it has been suggested that the ratio of these peptides to ACTH might be critical to maturation of foetal adrenal function¹¹. We have examined the ability of one of these peptides, αMSH, to influence adrenal function in the rabbit foetus. We present here evidence that the foetal adrenal secretes cortisol in response to αMSH at stages in pregnancy when it is unresponsive to ACTH, but as the sensitivity to ACTH increases, the relative response to αMSH is diminished.