Early androgen activity after birth determines the hypothalamic expression of androgen and estrogen receptors in adulthood in female but not in male rats

TL;DR

The study shows that early androgen activity in female rats affects the development of hormone receptors in the brain, but not in males.

Contribution

The study reveals sex-specific effects of early androgen activity on hypothalamic steroid receptor expression in adulthood.

Findings

Early androgen activity influences hypothalamic hormone receptor expression in females but not in males.

Blocking androgen activity in early life increases estrogen receptor beta in female rats.

Testosterone levels in adulthood are affected by early androgenic activity in females.

Abstract

Gonadal steroids are involved in the organization and programming of several neural systems. The main objective of this study was to determine whether androgen activity in the early postnatal stage influenced the long-term expression of androgen and estrogen receptors in the hypothalamus. Androgen receptors (AR) and the main metabolic pathways of testosterone were inhibited using Flutamide, an AR inhibitor, Letrozole, an aromatase inhibitor, or Finasteride, a 5-alpha-reductase inhibitor, during the first five days of life in male and female Wistar rats. Hypothalamic hormonal receptors AR, and estradiol receptors (ER)α, and ERβ were analyzed by qPCR, and circulating hormone levels (testosterone, DHT, and estradiol) were measured using ELISA assay at P90. The inhibition of AR, 5α-reductase or aromatase did not alter the hypothalamic levels of hormone receptors in males. However, in females, blocking the androgen receptor increased the ERβ, while the inhibition of 5α-reductase decreased the ERα and the inhibition of aromatase increased AR and ERβ hypothalamic mRNA levels. Moreover, testosterone plasma levels decreased significantly in females independent of whether the AR, 5α-reductase, or aromatase were inhibited. However, only the inhibition of aromatase decreased circulating testosterone levels in males. Furthermore, higher plasma testosterone and DHT levels were detected in males compared to females. Our results highlight the influence of androgen activity during the first days of life in females on the long-term expression of androgen and estrogen receptors in the hypothalamus, which reaffirms the importance of studying both sexes to accurately explain the processes that determine the programming of neural systems during development.

Early postnatal androgenic activity programs steroid receptors in females.

Male sex steroid receptors do not depend on early postnatal androgenic activity.

Testosterone levels in adulthood depend on postnatal androgenic activity in females.

Androgenic activity differentially alters sex steroid receptors in the hypothalamus.

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