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

Mar 19, 2016Endocrinology

Estrogen’s role in developing specific adrenal zones before birth affects hormone production and stress response in adult female primates

AI simplified

Circadian Biology on OpenScience ↗PubMed ↗DOI ↗

Abstract

The slope of serum dehydroepiandrosterone sulfate (DHAS) decline with age was significantly steeper in letrozole-treated baboons compared to untreated ones, measured at -0.54 ± 0.005 versus -0.32 ± 0.003.

Increased fetal zone volume and serum DHAS levels were observed in baboons with suppressed estradiol due to letrozole treatment.
Letrozole treatment resulted in lower serum DHAS levels at various age intervals compared to untreated offspring.
The cortisol to DHAS ratio was higher in letrozole-treated offspring than in untreated ones.
ACTH stimulation increased cortisol and DHAS in untreated baboons but only cortisol in letrozole-treated offspring.
The findings suggest that fetal exposure to estradiol may influence the postnatal development of adrenal hormone production.

AI simplified

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.

Full Text

Full text is available at the source.

View full text ↗

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

Full Text

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the circadian biology brief

Abstract

Full Text

Related papers

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the circadian biology brief