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Abstract

Central modifications of allopregnanolone and ß-endorphin following subcutaneous administration of Nestorone (HTML) 
Lenzi,E.; Pluchino,N.; Begliuomini,S.; Casarosa,E.; Merlini,S.; Giannini,A.; Luisi,M.; Kumar,Narender; Sitruk-Ware,Regine; Genazzani,Andrea R.
Journal of Steroid Biochemistry and Molecular Biology 116(1-2): 15-20
Publication date: 2009

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The aim of the present study was to evaluate the potential action of Nestorone (alone or in combination with estradiol valerate) on the level of allopregnanolone and of the opioid ß-endorphin in selected brain areas.Wistar ovariectomized rats were given 0.05 mg/(kg day) of estradiol valerate (E2V) or subcutaneous Nestorone at three dose levels: low dose (10 µg/(kg day), antiovulatory dose (50 µg/(kg day) and high dose (250 µg/(kg day) with and without E2V.E2V therapy reversed the reduction of allopregnanolone and ß-endorphin induced by ovariectomy anywhere was analyzed except for the adrenal gland. Nestorone showed no effect on allopregnanolone concentration in serum or any part of the brain tissue when given alone while it had a synergistic increasing effect in allopregnanolone concentration in some parts of the brain (hippocampus, hypothalamus, anterior pituitary and serum) when given at high dose of 250 µg/(kg day) in combination with E2V. At lower doses it possesses a synergistic effect with E2V only in the hippocampus (at 50 µg/(kg day) and in the anterior pituitary (at 10 and 50 µg/(kg day).Nestorone administered alone at any dose led to significant increase in ß-endorphin levels in the hippocampus only while, in the high dose group, there was a significant increase in endorphin levels in anterior pituitary and hypothalamus in addition to hippocampus as compared to ovariectomized control rats. In addition, only the highest dose of Nestorone added to estrogen increased ß-endorphin levels of hippocampus and plasma. Thus the lower doses of Nestorone alone or in combination with estrogen do not seem to exert any great effect on both allopregnanolone and ß-endorphin. It is only the highest dose of Nestorone that increases allopregnanolone and ß-endorphin levels in selected brain areas, which are the hippocampus, the hypothalamus, the anterior pituitary and serum/plasma. This suggests that Nestorone at the antiovulatory dose levels may not alter the positive effects of estrogen treatment on mood and behaviour.

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