title: Allopregnanolone, a GABAA receptor agonist, decreases gonadotropin levels in women. A preliminary study.
abstract: Animal studies suggest regulatory effects on the hypothalamic-pituitary-gonad axis by allopregnanolone, an endogenous gamma-aminobutyric acid A (GABA(A)) receptor agonist. Elevated levels of allopregnanolone in women with hypothalamic amenorrhea have been seen. Isoallopregnanolone is an isomer to allopregnanolone, but without GABA(A) receptor effects. The purpose of this study was to investigate effects of allopregnanolone and isoallopregnanolone on gonadotropin levels in healthy women of fertile age. Ten women were given allopregnanolone and five women isoallopregnanolone intravenously in follicular phase. Repeated blood samples were drawn during the test day. Main outcomes were changes in serum levels of follicle-stimulating hormone (FSH), luteinising hormone (LH), oestradiol, and progesterone. Serum-FSH decreased between 5 and 105 min after the allopregnanolone injection (F(16,144)=2.18, p=0.008). Serum-LH was reduced between 5 and 35 min following the allopregnanolone injection (F(16,144)=2.63, p=0.001). Serum-oestradiol and -progesterone were not significantly changed after allopregnanolone injections. No effect on gonadotropin levels were seen after administration of isoallopregnanolone. Allopregnanolone reduces FSH and LH levels in women and the effect might be mediated via a specific GABA(A) receptor activation since isoallopregnanolone lacked this effect. Although the number of women was small, the results suggest a regulatory mechanism on the hypothalamic-pituitary-gonadal axis by allopregnanolon.
authors.affiliation: Department of Clinical Science, Obstetrics and Gynaecology, Umeå Neurosteroid Research Centre, Umeå University, SE-901 85 Umeå, Sweden.
authors.forename: Erika
authors.initials: E
authors.lastname: Timby
authors.forename: Helena
authors.initials: H
authors.lastname: Hedström
authors.forename: Torbjörn
authors.initials: T
authors.lastname: Bäckström
authors.forename: Inger
authors.initials: I
authors.lastname: Sundström-Poromaa
authors.forename: Sigrid
authors.initials: S
authors.lastname: Nyberg
authors.forename: Marie
authors.initials: M
authors.lastname: Bixo
mesh_terms: D000328:Adult; D015536:Down-Regulation / Q000187:drug effects; D004958:Estradiol / Q000097:blood; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D005498:Follicular Phase / Q000097:blood / Q000187:drug effects; D058785:GABA-A Receptor Agonists / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D006062:Gonadotropins / Q000097:blood*; D006801:Humans; D007275:Injections, Intravenous; D007986:Luteinizing Hormone / Q000097:blood; D010865:Pilot Projects; D011280:Pregnanolone / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000494:pharmacology*; D011374:Progesterone / Q000097:blood; D013997:Time Factors; D055815:Young Adult
chemical_list: D058785:GABA-A Receptor Agonists; D006062:Gonadotropins; D011374:Progesterone; D004958:Estradiol; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D011280:Pregnanolone