GABA-steroid effects in healthy subjects and women with polycystic ovary syndrome

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Hedström, HelenaUmeå universitet,Obstetrik och gynekologi (författare)

GABA-steroid effects in healthy subjects and women with polycystic ovary syndrome

BokEngelska2011

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Umeå :Umeå University,2011
70 s.
electronicrdacarrier

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LIBRIS-ID:oai:DiVA.org:umu-49375
ISBN:9789174593099
https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-49375URI

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Språk:engelska
Sammanfattning på:engelska

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Ämneskategori:vet swepub-contenttype
Ämneskategori:dok swepub-publicationtype

Varianttitlar

GABA-steroid effects :in healthy subjects and women with polycystic ovary syndrome

Serie

Umeå University medical dissertations,0346-6612 ;1455

Anmärkningar

Background: The progesterone metabolite allopregnanolone is involved in several clinical conditions in women, e.g. premenstrual dysphoric disorder. It is a very potent GABA-steroid with GABA-A receptor effects similar to other GABA-agonists, e.g. benzodiazepines, and it causes sedation. An objective way to examine effects on the GABA-A receptor in humans is to measure saccadic eye velocity (SEV), which is reduced by GABA-agonists, e.g. allopregnanolone. Animal studies suggest that allopregnanolone is involved in the regulation of gonadotropin secretion via the GABA-A receptor, but this has not been studied in humans. Polycystic ovary syndrome (PCOS) is the most common endocrine disturbance among women of fertile age (5–10%), characterized by polycystic ovaries, menstrual dysfunction, hyperandrogenity, and 50% have obesity. Studies have shown higher allopregnanolone levels in overweight people. PCOS women have increased levels of androstanediol, an androgen metabolite which is an GABA-A receptor agonist. Tolerance often occurs when persons are exposed to high levels of GABAergic modulators. It has not been studied whether GABA-A receptor sensitivity in PCOS women is changed. Another progesterone metabolite, isoallopregnanolone, is the stereoisomere of allopregnanolone but has not been shown to have any GABA-A receptor effect of its own. Instead it has often been used to control steroid specificity to allopregnanolone. Aims: To compare the effects of allopregnanolone and isoallopregnanolone on gonadotropin secretion. To compare allopregnanolone levels, GABA-A receptor sensitivity to allopregnanolone and effects on gonadotropin secretion in both cycle phases and PCOS conditions. To examine pharmacokinetics and pharmacodynamic properties for isoallopregnanolone. Method: In the follicular phase healthy women were examined for the effect of allopregnanolone or isoallopregnanolone on gonadotropin secretion. PCOS women and healthy women in both cycle phases were given allopregnanolone and the differences in effects on SEV were examined, as well as changes in serum levels of gonadotropins and allopregnanolone at baseline and during the test day. Pharmacokinetics and GABA-A receptor sensitivity using SEV were explored for isoallopregnanolone in healthy women. Results: Allopregnanolone decreases gonadotropin serum levels in healthy controls in both cycle phases, but has no effect on gonadotropin secretion in women with PCOS. PCOS women have higher baseline serum levels of allopregnanolone than follicular phase controls, but lower levels than luteal phase controls. PCOS women show greater reduction in SEV to allopregnanolone than controls. Isoallopregnanolone has no effect on gonadotropin secretion. There is an effect of isoallopregnanolone on SEV, explained by a metabolism of isoallopregnanolone into allopregnanolone. Conclusion: There are significant differences in the GABA-A receptor response to a GABA-steroid in different endocrine conditions in women of fertile age examined with saccadic eye velocity. The GABA-steroid allopregnanolone decreases gonadotropin serum levels in healthy women but not in PCOS women. The lack of effect on gonadotropins by isoallopregnanolone suggests an involvement of the GABA-A receptor.

Ämnesord och genrebeteckningar

MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Reproduktionsmedicin och gynekologi hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Obstetrics, Gynaecology and Reproductive Medicine hsv//eng
Allopregnanolone
isoallopregnanolone
gonadotropins
GABA-A receptor
women
polycystic ovary syndrome
saccade
obstetrik och gynekologi
Obstetrics and Gynaecology

Biuppslag (personer, institutioner, konferenser, titlar ...)

Bäckström, Torbjörn,professorUmeå universitet,Obstetrik och gynekologi(Swepub:umu)toba0001 (preses)
Bixo, Marie,ProfessorUmeå universitet,Obstetrik och gynekologi(Swepub:umu)mabi0001 (preses)
Milsom, Ian,ProfessorKliniska vetenskaper, avd för obstetrik och gynekologi, Göteborgs Universitet, Göteborg, Sverige (opponent)
Umeå universitetObstetrik och gynekologi (creator_code:org_t)

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MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Klinisk medicin; och Reproduktionsmed ...

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Av lärosätet: Umeå universitet

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