Allopregnanolone Alters the Luteinizing Hormone, Prolactin, and Progesterone Serum Levels Interfering with the Regression and Apoptosis in Rat Corpus Luteum

Abstract

Steroids synthesized in the central nervous system are termed "neurosteroids". They are synthesized and metabolized in several brain areas. The objective of this work was to determine if 1 intracerebroventricular allopregnanolone injection in rats can interfere in luteal regression in a close relationship with modifications in LH, progesterone, and prolactin serum concentrations. Allopregnanolone was injected during proestrus morning and the animals were sacrificed on oestrous morning. Ovulation test and histological analysis were performed in the oestrus morning with light and electron microscopy. Serum prolactin, LH, and progesterone levels were measured by radioimmunoassay. The allopregnanolone injection significantly decreased luteinizing hormone serum level and the number of oocytes on oestrus. Progesterone and prolactin serum levels were increased after this injection. The inhibition of apoptotic figures due to allopregnanolone administration was detected in the already formed corpora lutea belonging to the previous ovary cycle and it was significantly lower than in vehicle group (control). When the GABA(A) antagonist (bicuculline) was administered alone or previously to allopregnanolone, no effect on the ovulation rate was observed. No changes in the apoptotic cell numbers were observed with respect to those of vehicle group. These results show that the effect of centrally injected allopreganolone over reproductive function could be due to a centrally originated LH mediated effect over ovarian function that affects luteal regression, through the inhibition of apoptosis and stimulation of progesterone and prolactin release.

Neuroendocrine Regulation of Anxiety: Beyond the Hypothalamic‐Pituitary‐Adrenal Axis

“…However, the short half‐life of allopregnanolone and other inhibitory neurosteroids serves as a hindrance to their efficacy in the treatment of anxiety. Furthermore, exogenous allopregnanolone has been shown to impair ovarian function in the rat , suggesting that there may be a need for alternative approaches to elevating neurosteroid levels. Synthetic analogues such as ganaloxone have shown sedative, anxiolytic and anticonvulsant effects .…”

Effect of progesterone and first evidence about allopregnanolone action on the progression of epithelial human ovarian cancer cell lines

“…In fact, it is known that the concentration of ALLO and P4 varies during the estrous cycle and pregnancy in a similar manner. We have reported that intra-cerebroventricular (ICV) administration of ALLO modulates the hypothalamic-pituitary-gonadal axis and induces morpho-physiological changes at the ovarian level [15][16][17][18]. ALLO induces a reduction in nuclear proliferation cell antigen expression, accompanied by an increase in apoptosis of granulosa cells stimulating follicular atresia.…”

Progesterone Exerts a Neuromodulatory Effect on Turning Behavior of Hemiparkinsonian Male Rats: Expression of 3α-Hydroxysteroid Oxidoreductase and Allopregnanolone as Suggestive ofGABAAReceptors Involvement

“…Control animals were injected with sterile saline with 1% propylene glycol. The 4.9 μ M concentration of the GABA A receptor antagonist bicuculline was the same used in our previous published results [ 20 ].…”

“…We have previously demonstrated that the neuroactive steroids progesterone and ALLO modulate striatal dopaminergic activity of rats under different gonadal hormonal conditions [ 19 , 20 ] and that systemic administration of progesterone to hemiparkinsonian rats prevents depression-like behavior [ 21 ]. These beneficial premotor effects led us to inquire whether or not the neuroprotective effects of progesterone and/or its metabolite ALLO on premotor conditions could be extended to motor manifestations in a model of hemiparkinsonism in rats.…”