Increasing fetal adrenal formation of cortisol from pregnenolone during baboon (Papio papio) gestation

Abstract

To determine the maturational changes leading to adrenocortical self-sufficiency in baboon neonates, fetal adrenal growth and cortisol (F) production, in vivo, from pregnenolone (P5), progesterone (P4) and 11-deoxycortisol (S) were examined at various times during gestation. Adrenal weight of animals delivered prematurely (100-179 days gestation, term = 184) by cesarean section (N = 17) or spontaneously (N = 13) at term (181 ± 4 days, ̄x ± SE), tripled during the second half of gestation (r = 0.82; P<0.001; Y = 403e(0.017X)) and resulted primarily from growth of cortical fetal zone tissue. F production from [3H]P5, [3H]P4 or [3H]S (15 μci, 10 μg) by 50 mg homogenized tissue from selected glands incubated with NADPH was determined following extraction, and purification of [3H]F. Results were combined from animals delivered by cesarean section 84 to 54 days (N = 4), or 24 to 17 days prior to term (N = 3) and from neonates 1 day old (N = 3) or 5 and 12 days old (N = 2). F production from S (68.2% ± 13.1%, ̄x ± SE) and P4 (42.4% ± 2.9%) either remained constant or decreased during the study period, while that from P5 (6.9% ± 1.9%) increased (P<0.001) from 3 ± 1 pmole/mg at midgestation to 14 ± 5 pmole/mg shortly before term, reaching 51 ± 13 pmole/mg 1 day after spontaneous delivery. When corrected for adrenal weight, F production from S (88-118 nmole/2 adrenals) and P4 (46-77 nmole/2 adrenals) remained constant whereas that from P5 increased (P<0.001) from 0.3 ± 0.1 nmole/2 adrenals at midgestation to 17 ± 5 nmole/2 adrenals 1 day after spontaneous delivery. This capacity was maintained in the first 12 days of life. Thus fetal adrenal 3β-hydroxysteroid dehydrogenase-isomerase activity is increased, while 11β-, 17α- and 21-hydroxylase activities are relatively greater but unchanged during gestation. It is concluded that increased 3β-hydroxysteroid dehydrogenase-isomerase combined with adrenal growth permits increased utilization of P5 for F synthesis towards term. These changes may be important in ensuring adrenocortical self-sufficiency when, after delivery, placental P4 is no longer available for F production.