Premium
Constitutive expression of Steroidogenic factor‐1 (NR5A1) disrupts ovarian functions, fertility, and metabolic homeostasis in female mice
Author(s) -
Rotgers Emmi,
Nicol Barbara,
Rodriguez Karina,
Rattan Saniya,
Flaws Jodi A.,
Yao Humphrey HungChang
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.202100304r
Subject(s) - steroidogenic factor 1 , endocrinology , medicine , biology , homeostasis , hyperandrogenism , steroidogenic acute regulatory protein , glucose homeostasis , hormone , insulin resistance , polycystic ovary , insulin , gene expression , transcription factor , gene , biochemistry , nuclear receptor
Steroid hormones regulate various aspects of physiology, from reproductive functions to metabolic homeostasis. Steroidogenic factor‐1 (NR5A1) plays a central role in the development of steroidogenic tissues and their ability to produce steroid hormones. Inactivation of Nr5a1 in the mouse results in a complete gonadal and adrenal agenesis, absence of gonadotropes in the pituitary and impaired development of ventromedial hypothalamus, which controls glucose and energy metabolism. In this study, we set out to examine the consequences of NR5A1 overexpression (NR5A1+) in the NR5A1‐positive cell populations in female mice. Ovaries of NR5A1+ females presented defects such as multi‐oocyte follicles and an accumulation of corpora lutea. These females were hyperandrogenic, had irregular estrous cycles with persistent metestrus and became prematurely infertile. Furthermore, the decline in fertility coincided with weight gain, increased adiposity, hypertriglyceridemia, hyperinsulinemia, and impaired glucose tolerance, indicating defects in metabolic functions. In summary, excess NR5A1 expression causes hyperandrogenism, disruption of ovarian functions, premature infertility, and disorders of metabolic homeostasis. This NR5A1 overexpression mouse provides a novel model for studying not only the molecular actions of NR5A1, but also the crosstalk between endocrine, reproductive, and metabolic systems.