Central modifications of allopregnanolone and beta-endorphin following subcutaneous administration of Nestorone.
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 beta-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 microg/(kg day)), antiovulatory dose (50 micro/(kg day)) and high dose (250 microg/(kg day)) with and without E2V. E2V therapy reversed the reduction of allopregnanolone and beta-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 microg/(kg day) in combination with E2V. At lower doses it possesses a synergistic effect with E2V only in the hippocampus (at 50 microg/(kg day)) and in the anterior pituitary (at 10 and 50 microg/(kg day)). Nestorone administered alone at any dose led to significant increase in beta-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 beta-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 beta-endorphin. It is only the highest dose of Nestorone that increases allopregnanolone and beta-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.
Lenzi
E
E
Department of Reproductive Medicine and Child Development, Division of Gynaecology and Obstetrics, University of Pisa, Via Roma 35, 56100 Pisa, Italy.
Pluchino
N
N
Begliuomini
S
S
Casarosa
E
E
Merlini
S
S
Giannini
A
A
Luisi
M
M
Kumar
N
N
Sitruk-Ware
R
R
Genazzani
A R
AR
D000818:Animals; D001921:Brain / Q000378:metabolism; D003271:Contraceptive Agents, Female / Q000008:administration & dosage*; D005260:Female; D006624:Hippocampus / Q000378:metabolism; D007031:Hypothalamus / Q000378:metabolism; D055104:Infusions, Subcutaneous; D023421:Models, Animal; D018377:Neurotransmitter Agents / Q000378:metabolism*; D009653:Norprogesterones / Q000008:administration & dosage*; D010052:Ovariectomy; D011280:Pregnanolone / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D001615:beta-Endorphin / Q000378:metabolism*
D003271:Contraceptive Agents, Female; D018377:Neurotransmitter Agents; D009653:Norprogesterones; D001615:beta-Endorphin; C029167:ST 1435; D011280:Pregnanolone