Developmental expression of and effect of betamethasone on the messenger ribonucleic acid levels for peptide growth factors in the baboon fetal adrenal gland

Abstract

In the present study, we determined whether expression of the messenger ribonucleic acids (mRNAs) for insulin-like growth factor-II (IGF-II), and its principal IGF type-1 receptor and IGF-binding protein-2 (IGFBP-2), as well as basic fibroblast growth factor (bFGF), was developmentally regulated in the baboon fetal adrenal gland. In the second phase of this study, fetal pituitary ACTH was suppressed by the administration of betamethasone to determine the possible effect on the mRNA levels for those factors, i.e. IGF-II and IGFBP-2, shown to be expressed at high levels in the adrenal late in fetal development. Adrenals were obtained from fetuses delivered via Cesarean section on days 60 (early), 100 (mid), and 165 (late) of gestation (term=184 days) from untreated baboons and on day 165 from baboons in which betamethasone was administered to the fetus, or to fetus and mother, every other day between days 150 and 164 of gestation. Although the mRNA levels of IGF-II in the fetal adrenal were similar at early, mid and late gestation, IGF type-1 receptor mRNA levels were approximately 2-to 3-fold greater (P<0·01) at mid than at early or late gestation. In contrast, there was an increase (P<0·001) in fetal adrenal IGFBP-2 and bFGF mRNA levels in late gestation. Although fetal adrenal weights and width of the zone of definitive/transitional cells exhibiting immunocytochemical staining for 5 -3 -hydroxysteroid dehydrogenase (3 -HSD) were markedly suppressed (P<0·01) by the administration of betamethasone, IGF-II and IGFBP-2 mRNA expression was not decreased. In summary, very different patterns of mRNA levels for IGF-II, IGF type-1 receptor, IGFBP-2 and bFGF were exhibited in the developing baboon fetal adrenal gland, which may reflect functionally important differences in their respective cellular localization within the cortex, as well as a divergence in the functional development of the fetal, transitional and definitive zones of the baboon fetal adrenal cortex.

Extracellular signal-regulated kinases (ERK1/2) signaling pathway plays a role in cortisol secretion in the long-term hypoxic ovine fetal adrenal near term

“…Surprisingly, we noted robust basal phosphorylation of both ERK1 and ERK2 in both LTH and control FACs, perhaps reflecting the mitotically active nature of the FACs. Elevated levels of growth factors observed during development (1,20,26) or NH 2 -terminal POMC-derived peptides may contribute to the enhanced level of phosphorylation. In response to UO126 inhibition of ERK1/2 we noted a profound inhibitory effect on both ACTH and 8-bromo-cAMP stimulated cortisol biosynthesis in both groups, virtually eliminating the ability to produce cortisol in response to ACTH and cAMP in control FACs while severely blunting the response in the LTH FAC.…”

Developmental expression of cell cycle regulators in the baboon fetal adrenal gland

“…Other peptides of placental or fetal origin, e.g. epidermal growth factor and fibroblast growth factor, also appear to have a role in growth of the primate fetal adrenal , Simonian & Gill 1981, Aberdeen et al 1999. Therefore, it is apparent that regulation of fetal adrenocortical growth and maturation is a complex process involving fetal pituitary peptides, placental estrogen, and fetal growth factors, which act/interact to regulate mitosis and hypertrophy.…”