Activation of the baboon fetal pituitary-adrenocortical axis at midgestation by estrogen: responsivity of the fetal adrenal gland to adrenocorticotropic hormone in vitro.
We have previously demonstrated that increased expression of fetal pituitary proopiomelanocortin mRNA and the induction of enzymes catalyzing fetal adrenal cortisol formation at term are regulated by estrogen-induced changes in placental oxidation of maternal cortisol to cortisone. To test the hypothesis that induction of fetal pituitary adrenocorticotropic hormone (ACTH) production by estrogen-induced changes in placental cortisol oxidation results in increased responsivity of the fetal adrenal gland to ACTH, in the present study we compared fetal adrenal sensitivity to ACTH in vitro at midgestation in untreated controls and in animals treated at this time in gestation with estrogen. Fetal adrenals were obtained on Day 100 (n = 7) and Day 165 (n = 5; term = Day 184) from untreated baboons and on Day 100 following maternal treatment with estradiol (s.c.; Days 70-100; n = 10) or androgen precursor (n = 3). Adrenal slices (15-25 mg) were perifused (100 microliters/min; 37 degrees C) with Medium 199 (no phenol red); media were collected at 10-min intervals and assayed for cortisol and dehydroepiandrosterone. Secretion of cortisol and dehydroepiandrosterone reached equilibrium after 140 min of perifusion; therefore, basal release was calculated as the mean steroid concentrations during 190-240 min. Adrenal slices were then perifused for 20 min with saline or ACTH at 240 (0.001 nmol), 370 (0.01 nmol), and 490 (0.1 nmol) min, and an overall average cortisol/dehydroepiandrosterone secretion rate (pg/min/mg) between 240-600 min was calculated.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Physiology, Eastern Virginia Medical School, Norfolk 23501-1980, USA.
K A
KA
Berghorn
E D
ED
Albrecht
G J
GJ
Pepe
D000302:Adrenal Cortex / Q000187:drug effects* / Q000196:embryology* / Q000378:metabolism; D000324:Adrenocorticotropic Hormone / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D003687:Dehydroepiandrosterone / Q000378:metabolism; D004958:Estradiol / Q000097:blood / Q000494:pharmacology*; D005260:Female; D005865:Gestational Age; D006854:Hydrocortisone / Q000378:metabolism; D066298:In Vitro Techniques; D009929:Organ Size; D010215:Papio; D010477:Perfusion; D010902:Pituitary Gland / Q000187:drug effects* / Q000196:embryology* / Q000502:physiology; D011247:Pregnancy
D003687:Dehydroepiandrosterone; D004958:Estradiol; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone