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Effects of estradiol and raloxifene analog on brain, adrenal and serum allopregnanolone content in fertile and ovariectomized female rats.
Neuroendocrinology. 2000 Sep; 72(3):162-70.N

Abstract

Allopregnanolone is a neuroactive steroid synthesized in rat gonads, adrenal cortex, and central nervous system. It has been suggested that sex steroid hormones might influence allopregnanolone concentrations but no clear data have ever been reported. The aim of the present study was to investigate the effects of administration of 17beta-estradiol (17beta-E2), the raloxifene analog LY-117018 or their combination on allopregnanolone levels in fertile and ovariectomized (OVX) rats. Thirteen groups of 12 Wistar female rats each received either 17beta-E2 (0.1 or 1 microg/day) or LY-117018 (25, 250, and 1,250 microg/day), or 17beta-E2 1 microg/day plus LY-117018: 25, 250, and 1,250 microg/day for 14 days. The rats were then sacrificed and allopregnanolone content was assessed in the hypothalamus, hippocampus, pituitary, adrenals, and serum. Ovariectomy determined a significant decrease in allopregnanolone content in the hypothalamus, hippocampus, pituitary, and serum, while increasing it in the adrenals (p<0.01). In OVX rats, the administration of either 17beta-E2 or LY- 117018 restored ovariectomy-induced allopregnanolone changes. The administration of LY-117018 in addition to 17beta-E2 to OVX animals suppressed the increase in allopregnanolone levels determined by 17beta-E2 in the hippocampus, hypothalamus, and pituitary, but not in the adrenals and serum. In fertile rats, the administration of LY-117018 reproduced the effects of ovariectomy. This study shows that the raloxifene analog LY-117018 has an estrogen-like action on the central nervous system of OVX rats when administered alone, while it acts as an antiestrogen in the presence of 17beta-E2, both in OVX animals treated with 17beta-E2 and in fertile rats. A different effect was observed in the adrenal glands. The mechanism of action of this compound has still to be clarified.

Authors+Show Affiliations

Department of Reproductive Medicine and Child Development, Division of Obstetrics and Gynecology, University of Pisa, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

11025410

Citation

Genazzani, A R., et al. "Effects of Estradiol and Raloxifene Analog On Brain, Adrenal and Serum Allopregnanolone Content in Fertile and Ovariectomized Female Rats." Neuroendocrinology, vol. 72, no. 3, 2000, pp. 162-70.
Genazzani AR, Bernardi F, Stomati M, et al. Effects of estradiol and raloxifene analog on brain, adrenal and serum allopregnanolone content in fertile and ovariectomized female rats. Neuroendocrinology. 2000;72(3):162-70.
Genazzani, A. R., Bernardi, F., Stomati, M., Monteleone, P., Luisi, S., Rubino, S., Farzati, A., Casarosa, E., Luisi, M., & Petraglia, F. (2000). Effects of estradiol and raloxifene analog on brain, adrenal and serum allopregnanolone content in fertile and ovariectomized female rats. Neuroendocrinology, 72(3), 162-70.
Genazzani AR, et al. Effects of Estradiol and Raloxifene Analog On Brain, Adrenal and Serum Allopregnanolone Content in Fertile and Ovariectomized Female Rats. Neuroendocrinology. 2000;72(3):162-70. PubMed PMID: 11025410.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of estradiol and raloxifene analog on brain, adrenal and serum allopregnanolone content in fertile and ovariectomized female rats. AU - Genazzani,A R, AU - Bernardi,F, AU - Stomati,M, AU - Monteleone,P, AU - Luisi,S, AU - Rubino,S, AU - Farzati,A, AU - Casarosa,E, AU - Luisi,M, AU - Petraglia,F, PY - 2000/10/12/pubmed PY - 2001/2/28/medline PY - 2000/10/12/entrez SP - 162 EP - 70 JF - Neuroendocrinology JO - Neuroendocrinology VL - 72 IS - 3 N2 - Allopregnanolone is a neuroactive steroid synthesized in rat gonads, adrenal cortex, and central nervous system. It has been suggested that sex steroid hormones might influence allopregnanolone concentrations but no clear data have ever been reported. The aim of the present study was to investigate the effects of administration of 17beta-estradiol (17beta-E2), the raloxifene analog LY-117018 or their combination on allopregnanolone levels in fertile and ovariectomized (OVX) rats. Thirteen groups of 12 Wistar female rats each received either 17beta-E2 (0.1 or 1 microg/day) or LY-117018 (25, 250, and 1,250 microg/day), or 17beta-E2 1 microg/day plus LY-117018: 25, 250, and 1,250 microg/day for 14 days. The rats were then sacrificed and allopregnanolone content was assessed in the hypothalamus, hippocampus, pituitary, adrenals, and serum. Ovariectomy determined a significant decrease in allopregnanolone content in the hypothalamus, hippocampus, pituitary, and serum, while increasing it in the adrenals (p<0.01). In OVX rats, the administration of either 17beta-E2 or LY- 117018 restored ovariectomy-induced allopregnanolone changes. The administration of LY-117018 in addition to 17beta-E2 to OVX animals suppressed the increase in allopregnanolone levels determined by 17beta-E2 in the hippocampus, hypothalamus, and pituitary, but not in the adrenals and serum. In fertile rats, the administration of LY-117018 reproduced the effects of ovariectomy. This study shows that the raloxifene analog LY-117018 has an estrogen-like action on the central nervous system of OVX rats when administered alone, while it acts as an antiestrogen in the presence of 17beta-E2, both in OVX animals treated with 17beta-E2 and in fertile rats. A different effect was observed in the adrenal glands. The mechanism of action of this compound has still to be clarified. SN - 0028-3835 UR - https://www.unboundmedicine.com/medline/citation/11025410/Effects_of_estradiol_and_raloxifene_analog_on_brain_adrenal_and_serum_allopregnanolone_content_in_fertile_and_ovariectomized_female_rats_ L2 - https://www.karger.com?DOI=10.1159/000054583 DB - PRIME DP - Unbound Medicine ER -