A single dose of allopregnanolone affects rat ovarian morphology and steroidogenesis

Abstract

Allopregnanolone, a progesterone metabolite, is one of the best characterized neurosteroids. In a dose that mimics serum levels during stress, allopregnanolone inhibits sexual receptivity and ovulation and induces a decrease in luteinizing hormone levels. The aim of this work was to examine the effect of an intracerebroventricular administration of allopregnanolone on ovarian morphophysiology, serum and tissue levels of progesterone and estrogen, and enzymatic activity of 3β-hydroxysteroid dehydrogenase, 20α-hydroxysteroid dehydrogenase and 3α-hydroxysteroid oxido-reductase in the ovary and in the medial basal hypothalamus on the morning of estrus. Ovarian morphology was analyzed under light microscopy. The hormone assays were performed by radioimmunoassay. The enzymatic activities were measured by spectrophotometric analysis. The morphometric analysis revealed that, in allopregnanolone-treated animals, the number of secondary and Graafian follicles was decreased while that of atretic follicles and cysts was significantly increased. Some cysts showed luteinized unruptured follicles. There were no differences in the number of tertiary follicles or corpora lutea in comparison with the corresponding control groups. In allopregnanolone-treated animals, progesterone serum levels were increased, while ovarian progesterone levels were decreased. Moreover, 3β-HSD and 3α-HSOR enzymatic activities were increased in the medial basal hypothalamus while ovarian levels were decreased. The enzyme 20α-hydroxysteroid dehydrogenase showed the opposite profile. The results of this study showed that allopregnanolone interferes on ovarian steroidogenesis and ovarian morphophysiology in rats, providing a clear evidence for the role of this neurosteroid in the control of reproductive function under stress situations.

Superior mesenteric ganglion neural modulation of ovarian angiogenesis, apoptosis and proliferation by the neuroactive steroid allopregnanolone

“…88 The contrary effects of ALLO 0.06 µm on the SMG-ONP-ovary system between the intrinsic and extrinsic apoptotic pathways could also be explained by a dual modulation of structures. Indeed, this has been observed after ALLO intracerebroventricular administration, 46 which led to an increased follicular apoptosis and luteolysis delay.…”

“…[40][41][42][43] In addition, its actions on the hypothalamic-pituitarygonadal axis affect the ovarian physiopathology. [44][45][46][47] The ovarian function is regulated by the hypothalamic-pituitarygonadal axis, which controls growth, differentiation and maturation of ovarian follicles and corpora lutea, ovulation, and hormone secretion. Gonadotropins are the main hormones that arrive at the ovary and exert their actions throughout the cycle.…”

Local effect of allopregnanolone in rat ovarian steroidogenesis, follicular and corpora lutea development

“…Moreover, it can modulate a variety of behaviors, such as reproductive 10 – 13 , social, exploratory and affective conducts 14 – 16 . Previous work from our laboratory reported ALLO actions over the hypothalamic–pituitary–gonadal axis when administered via ICV 17 – 19 and its effects on the ovarian peripheral innervation using an ex vivo culture of the superior mesenteric ganglion- ovarian nervous plexus—ovarian system 20 – 22 . These findings led us to consider ALLO not only as a modulator of central function but also of ovarian physiology.…”

“Rapid actions of the neurosteroid allopregnanolone on ovarian and hypothalamic steroidogenesis: Central and peripheral modulation”

“…Other related behavioural changes are anxiolysis and memory potentiation . In addition, the hypothalamus‐pituitary‐ovarian axis deregulation induced by ALLO administration, causes alterations in the endocrine serum profile and the ovarian morphophysiology …”