Effects of Estradiol and Raloxifene Analog on Brain, Adrenal and Serum Allopregnanolone Content in Fertile and Ovariectomized Female Rats
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...
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| Veröffentlicht in: | Neuroendocrinology 2000-09, Vol.72 (3), p.162-170 |
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| creator | Genazzani, Andrea R. Bernardi, Francesca Stomati, Massimo Monteleone, Patrizia Luisi, Stefano Rubino, Silvia Farzati, Angelo Casarosa, Elena Luisi, Michele Petraglia, Felice |
| description | 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 17β-estradiol (17β-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 17β-E2 (0.1 or 1 µg/day) or LY-117018 (25, 250, and 1,250 µg/day), or 17β-E2 1 µg/day plus LY-117018: 25, 250, and 1,250 µg/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 17β-E2 or LY- 117018 restored ovariectomy-induced allopregnanolone changes. The administration of LY-117018 in addition to 17β-E2 to OVX animals suppressed the increase in allopregnanolone levels determined by 17β-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 17β-E2, both in OVX animals treated with 17β-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. |
| doi_str_mv | 10.1159/000054583 |
| format | Article |
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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 17β-estradiol (17β-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 17β-E2 (0.1 or 1 µg/day) or LY-117018 (25, 250, and 1,250 µg/day), or 17β-E2 1 µg/day plus LY-117018: 25, 250, and 1,250 µg/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 17β-E2 or LY- 117018 restored ovariectomy-induced allopregnanolone changes. The administration of LY-117018 in addition to 17β-E2 to OVX animals suppressed the increase in allopregnanolone levels determined by 17β-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 17β-E2, both in OVX animals treated with 17β-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.</description><identifier>ISSN: 0028-3835</identifier><identifier>EISSN: 1423-0194</identifier><identifier>DOI: 10.1159/000054583</identifier><identifier>PMID: 11025410</identifier><identifier>CODEN: NUNDAJ</identifier><language>eng</language><publisher>Basel, Switzerland: S. Karger AG</publisher><subject>Adrenal Glands - drug effects ; Adrenal Glands - metabolism ; allopregnanolone ; Animals ; Brain - drug effects ; Brain - metabolism ; Drug Combinations ; Drug Interactions - physiology ; Estradiol - metabolism ; Estradiol - pharmacology ; Estrogen Antagonists - pharmacology ; Female ; Fertility - drug effects ; Fertility - physiology ; Hippocampus - drug effects ; Hippocampus - metabolism ; Hormone Actions on the Brain ; Hypothalamus - drug effects ; Hypothalamus - metabolism ; Ovariectomy - adverse effects ; Pituitary Gland - drug effects ; Pituitary Gland - metabolism ; Pregnanolone - biosynthesis ; Pregnanolone - blood ; Pyrrolidines - pharmacology ; raloxifene ; Raloxifene Hydrochloride - analogs & derivatives ; Rats ; Rats, Wistar ; Thiophenes - pharmacology</subject><ispartof>Neuroendocrinology, 2000-09, Vol.72 (3), p.162-170</ispartof><rights>2000 S. Karger AG, Basel</rights><rights>Copyright 2000 S. Karger AG, Basel.</rights><rights>Copyright S. Karger AG Sep 2000</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c386t-e397c9c9744072877550ed2af12819bf2cf248aa5306ce6b19606efd1f49fb1a3</citedby><cites>FETCH-LOGICAL-c386t-e397c9c9744072877550ed2af12819bf2cf248aa5306ce6b19606efd1f49fb1a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,2423,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11025410$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Genazzani, Andrea R.</creatorcontrib><creatorcontrib>Bernardi, Francesca</creatorcontrib><creatorcontrib>Stomati, Massimo</creatorcontrib><creatorcontrib>Monteleone, Patrizia</creatorcontrib><creatorcontrib>Luisi, Stefano</creatorcontrib><creatorcontrib>Rubino, Silvia</creatorcontrib><creatorcontrib>Farzati, Angelo</creatorcontrib><creatorcontrib>Casarosa, Elena</creatorcontrib><creatorcontrib>Luisi, Michele</creatorcontrib><creatorcontrib>Petraglia, Felice</creatorcontrib><title>Effects of Estradiol and Raloxifene Analog on Brain, Adrenal and Serum Allopregnanolone Content in Fertile and Ovariectomized Female Rats</title><title>Neuroendocrinology</title><addtitle>Neuroendocrinology</addtitle><description>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 17β-estradiol (17β-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 17β-E2 (0.1 or 1 µg/day) or LY-117018 (25, 250, and 1,250 µg/day), or 17β-E2 1 µg/day plus LY-117018: 25, 250, and 1,250 µg/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 17β-E2 or LY- 117018 restored ovariectomy-induced allopregnanolone changes. The administration of LY-117018 in addition to 17β-E2 to OVX animals suppressed the increase in allopregnanolone levels determined by 17β-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 17β-E2, both in OVX animals treated with 17β-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.</description><subject>Adrenal Glands - drug effects</subject><subject>Adrenal Glands - metabolism</subject><subject>allopregnanolone</subject><subject>Animals</subject><subject>Brain - drug effects</subject><subject>Brain - metabolism</subject><subject>Drug Combinations</subject><subject>Drug Interactions - physiology</subject><subject>Estradiol - metabolism</subject><subject>Estradiol - pharmacology</subject><subject>Estrogen Antagonists - pharmacology</subject><subject>Female</subject><subject>Fertility - drug effects</subject><subject>Fertility - physiology</subject><subject>Hippocampus - drug effects</subject><subject>Hippocampus - metabolism</subject><subject>Hormone Actions on the Brain</subject><subject>Hypothalamus - drug effects</subject><subject>Hypothalamus - metabolism</subject><subject>Ovariectomy - adverse effects</subject><subject>Pituitary Gland - drug effects</subject><subject>Pituitary Gland - metabolism</subject><subject>Pregnanolone - biosynthesis</subject><subject>Pregnanolone - blood</subject><subject>Pyrrolidines - pharmacology</subject><subject>raloxifene</subject><subject>Raloxifene Hydrochloride - analogs & derivatives</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Thiophenes - pharmacology</subject><issn>0028-3835</issn><issn>1423-0194</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2000</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNpt0U9rFDEUAPBQlHatPfQsSOhBEBzN38nkuC5bFUoL1Z6H7MzLkppJtsmMqN_Ab226u61QzCUh7_feI3kInVLynlKpP5CypJANP0AzKhivCNXiGZoRwpqKN1weoRc53xbFNGeH6IhSwqSgZIb-LK2Fbsw4WrzMYzK9ix6b0ONr4-NPZyEAnodyXuMY8MdkXHiH532Ccrd1XyFNA557HzcJ1sGE6GPJWcQwQhixC_gc0ug8bPXVD5NcaRgH9xv6EhpMiVybMb9Ez63xGU72-zG6OV9-W3yuLq4-fVnML6qON_VYAdeq051WQhDFGqWkJNAzYylrqF5Z1lkmGmMkJ3UH9YrqmtRge2qFtitq-DF6s6u7SfFugjy2g8sdeG8CxCm3VCnGyj8VePYE3sYplWfnlimhFKVCFvR2h7oUc05g201yg0m_Wkra--G0j8Mp9vW-4LQaoP8n99Mo4NUOfDdpDekRPKSf_Td6ubzcgnbTW_4Xhkad0Q</recordid><startdate>20000901</startdate><enddate>20000901</enddate><creator>Genazzani, Andrea R.</creator><creator>Bernardi, Francesca</creator><creator>Stomati, Massimo</creator><creator>Monteleone, Patrizia</creator><creator>Luisi, Stefano</creator><creator>Rubino, Silvia</creator><creator>Farzati, Angelo</creator><creator>Casarosa, Elena</creator><creator>Luisi, Michele</creator><creator>Petraglia, Felice</creator><general>S. 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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 17β-estradiol (17β-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 17β-E2 (0.1 or 1 µg/day) or LY-117018 (25, 250, and 1,250 µg/day), or 17β-E2 1 µg/day plus LY-117018: 25, 250, and 1,250 µg/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 17β-E2 or LY- 117018 restored ovariectomy-induced allopregnanolone changes. The administration of LY-117018 in addition to 17β-E2 to OVX animals suppressed the increase in allopregnanolone levels determined by 17β-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 17β-E2, both in OVX animals treated with 17β-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.</abstract><cop>Basel, Switzerland</cop><pub>S. Karger AG</pub><pmid>11025410</pmid><doi>10.1159/000054583</doi><tpages>9</tpages></addata></record> |
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| ispartof | Neuroendocrinology, 2000-09, Vol.72 (3), p.162-170 |
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| language | eng |
| recordid | cdi_pubmed_primary_11025410 |
| source | Karger Journals; MEDLINE |
| subjects | Adrenal Glands - drug effects Adrenal Glands - metabolism allopregnanolone Animals Brain - drug effects Brain - metabolism Drug Combinations Drug Interactions - physiology Estradiol - metabolism Estradiol - pharmacology Estrogen Antagonists - pharmacology Female Fertility - drug effects Fertility - physiology Hippocampus - drug effects Hippocampus - metabolism Hormone Actions on the Brain Hypothalamus - drug effects Hypothalamus - metabolism Ovariectomy - adverse effects Pituitary Gland - drug effects Pituitary Gland - metabolism Pregnanolone - biosynthesis Pregnanolone - blood Pyrrolidines - pharmacology raloxifene Raloxifene Hydrochloride - analogs & derivatives Rats Rats, Wistar Thiophenes - pharmacology |
| title | Effects of Estradiol and Raloxifene Analog on Brain, Adrenal and Serum Allopregnanolone Content in Fertile and Ovariectomized Female Rats |
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