Hypothalamic Expression of Estrogen Receptor Isoforms Underlies Estradiol Control of Luteinizing Hormone in Female Rats

Author:

Henriques Patricia C1,Aquino Nayara S S1,Campideli-Santana Ana C1,Silva Juneo F2,Araujo-Lopes Roberta1,Franci Celso R3,Coimbra Candido C1,Szawka Raphael E1ORCID

Affiliation:

1. Departamento de Fisiologia e Biofisica, Instituto de Ciencias Biologicas, Universidade Federal de Minas Gerais , 31270-901, Belo Horizonte , Brazil

2. Centro de Microscopia Eletronica, Departamento de Ciencias Biologicas, Universidade Estadual de Santa Cruz , Campus Soane Nazare de Andrade, 45662–900, Ilheus , Brazil

3. Departamento de Fisiologia, Faculdade de Medicina de Ribeirao Preto, 14049-900, Universidade de São Paulo , Ribeirao Preto , Brazil

Abstract

Abstract Luteinizing hormone (LH) secretion during the ovarian cycle is governed by fluctuations in circulating estradiol (E2) that oppositely regulate kisspeptin neurons in the anteroventral periventricular nucleus (AVPV) and arcuate nucleus (ARC) of the hypothalamus. However, how these effects are orchestrated to achieve fertility is unknown. Here, we have tested the hypothesis that AVPV and ARC neurons have different sensitivities to E2 to coordinate changes in LH secretion. Cycling and ovariectomized rats with low and high E2 levels were used. As an index of E2 responsiveness, progesterone receptor (PR) was expressed only in the AVPV of rats with high E2, showing the preovulatory LH surge. On the other hand, kisspeptin neurons in the ARC responded to low E2 levels sufficient to suppress LH release. Notably, the Esr1/Esr2 ratio of gene expression was higher in the ARC than AVPV, regardless of E2 levels. Accordingly, the selective pharmacological activation of estrogen receptor α (ERα) required lower doses to induce PR in the ARC. The activation of ERβ, in turn, amplified E2-induced PR expression in the AVPV and the LH surge. Thus, ARC and AVPV neurons are differently responsive to E2. Lower E2 levels activate ERα in the ARC, whereas ERβ potentiates the E2 positive feedback in the AVPV, which appears related to the differential Esr1/Esr2 ratio in these 2 brain areas. Our findings provide evidence that the distinct expression of ER isoforms in the AVPV and ARC plays a key role in the control of periodic secretion of LH required for fertility in females.

Publisher

The Endocrine Society

Subject

Endocrinology

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