title: Estrogen Regulation of Fetal Adrenal Cortical Zone-Specific Development in the Nonhuman Primate Impacts Adrenal Production of Androgen and Cortisol and Response to ACTH in Females in Adulthood.
abstract: We showed that the volume of the fetal zone of the fetal adrenal gland and serum dehydroepiandrosterone sulfate (DHAS) levels at term were increased in baboons in which estradiol levels were suppressed by treatment with aromatase inhibitor 4,4-[1,2,3-triazol-1yl-methylene] bis-benzonitrite (letrozole). The fetal zone remodels postnatally into the reticular zone and DHAS production, and serum levels decline with age. Therefore, we determined whether the trajectory of reticular zone DHAS secretion and response to ACTH were altered in offspring deprived of estrogen in utero. Female offspring were delivered to baboons untreated or treated daily throughout the second half of gestation with letrozole (estradiol reduced >95%) or letrozole plus estradiol and cortisol and DHAS determined in blood samples obtained bimonthly between 4 and 125 months and after iv bolus of ACTH. The slope/rate of decline in serum DHAS with advancing age was greater (P < .01) in letrozole-treated (-0.54 ± 0.005) than untreated (-0.32 ± 0.003) baboons and partially restored by letrozole-estradiol (-0.43 ± 0.004). Serum cortisol was similar and relatively constant in all offspring. Moreover, in letrozole-treated offspring, serum DHAS at 61-66, 67-95, and 96-125 months were lower (P < .05), and cortisol to DHAS ratio was greater (P < .05) than in untreated offspring. ACTH at high level increased cortisol and DHAS in untreated baboons and cortisol but not DHAS in letrozole-treated offspring. We propose that postnatal development of the primate adrenal cortex, including the decline in reticular zone DHAS production, response to ACTH and maintenance of cortisol to DHAS ratio with advancing age is modulated by exposure of the fetal adrenal to estradiol.
authors.affiliation: Departments of Physiological Sciences (G.J.P., T.J.L.) and Obstetrics and Gynecology (A.M.), Eastern Virginia Medical School, Norfolk, Virginia 23501; and Departments of Obstetrics/Gynecology/Reproductive Sciences and Physiology (G.A., E.D.A.), University of Maryland School of Medicine, Baltimore, Maryland 21201.
authors.forename: Gerald J
authors.initials: GJ
authors.lastname: Pepe
authors.affiliation: Departments of Physiological Sciences (G.J.P., T.J.L.) and Obstetrics and Gynecology (A.M.), Eastern Virginia Medical School, Norfolk, Virginia 23501; and Departments of Obstetrics/Gynecology/Reproductive Sciences and Physiology (G.A., E.D.A.), University of Maryland School of Medicine, Baltimore, Maryland 21201.
authors.forename: Adina
authors.initials: A
authors.lastname: Maniu
authors.affiliation: Departments of Physiological Sciences (G.J.P., T.J.L.) and Obstetrics and Gynecology (A.M.), Eastern Virginia Medical School, Norfolk, Virginia 23501; and Departments of Obstetrics/Gynecology/Reproductive Sciences and Physiology (G.A., E.D.A.), University of Maryland School of Medicine, Baltimore, Maryland 21201.
authors.forename: Graham
authors.initials: G
authors.lastname: Aberdeen
authors.affiliation: Departments of Physiological Sciences (G.J.P., T.J.L.) and Obstetrics and Gynecology (A.M.), Eastern Virginia Medical School, Norfolk, Virginia 23501; and Departments of Obstetrics/Gynecology/Reproductive Sciences and Physiology (G.A., E.D.A.), University of Maryland School of Medicine, Baltimore, Maryland 21201.
authors.forename: Terrie J
authors.initials: TJ
authors.lastname: Lynch
authors.affiliation: Departments of Physiological Sciences (G.J.P., T.J.L.) and Obstetrics and Gynecology (A.M.), Eastern Virginia Medical School, Norfolk, Virginia 23501; and Departments of Obstetrics/Gynecology/Reproductive Sciences and Physiology (G.A., E.D.A.), University of Maryland School of Medicine, Baltimore, Maryland 21201.
authors.forename: Eugene D
authors.initials: ED
authors.lastname: Albrecht
mesh_terms: D000311:Adrenal Glands / Q000187:drug effects* / Q000378:metabolism; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000728:Androgens / Q000097:blood*; D000818:Animals; D047072:Aromatase Inhibitors / Q000494:pharmacology; D019314:Dehydroepiandrosterone Sulfate / Q000097:blood; D004958:Estradiol / Q000097:blood*; D005260:Female; D005333:Fetus / Q000187:drug effects* / Q000378:metabolism; D006854:Hydrocortisone / Q000097:blood*; D000077289:Letrozole; D009570:Nitriles / Q000494:pharmacology; D010215:Papio; D011388:Prolactin / Q000097:blood; D014230:Triazoles / Q000494:pharmacology
chemical_list: D000728:Androgens; D047072:Aromatase Inhibitors; D009570:Nitriles; D014230:Triazoles; D004958:Estradiol; D019314:Dehydroepiandrosterone Sulfate; D000077289:Letrozole; D000324:Adrenocorticotropic Hormone; D011388:Prolactin; D006854:Hydrocortisone