Allopregnanolone, a GABA_A 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.

Keywords:

• FSH
• LH
• GABA
• allopregnanolone
• isoallopregnanolone

Acknowledgements

The antiserum used in the allopregnanolone RIA was a kind gift from Professor R. D. Purdy, Department of Neuropharmacology, The Scripps Research Institute, La Jolla, CA, USA. Mrs. Elisabeth Zingmark and Ms. Agneta Andersson are recognized for excellent laboratory work. This study was supported by grants from the Swedish Research Council, medicine proj. 4X-11198, EU structural fund objective 1 program, Umeå University Foundations, Västerbottens läns landsting, Umeå kommun, the Astrid Karlsson Foundation, and the Tore Nilsson Foundation. The authors declare no other financial interests relevant to the present study.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.