Allopregnanolone, a GABA_A receptor agonist, decreases gonadotropin levels in women. A preliminary study

References

• Santoro N, Filicori M, Crowley WF Jr. Hypogonadotropic disorders in men and women: diagnosis and therapy with pulsatile gonadotropin-releasing hormone. Endocr Rev 1986;7:11–23.
   PubMed Web of Science ®Google Scholar
• Calogero AE, Palumbo MA, Bosboom AMJ, Burrello N, Ferrara E, Palumbo G, Petraglia F, D'Agata R. The neuroactive steroid allopregnanolone suppresses hypothalamic gonadotropin-releasing hormone release through a mechanism mediated by the gamma-aminobutyric acidA receptor. J Endocrinol 1998;158:121–125.
   PubMed Web of Science ®Google Scholar
• Sim JA, Skynner MJ, Herbison AE. Direct regulation of postnatal GnRH neurons by the progesterone derivative allopregnanolone in the mouse. Endocrinology 2001;42:4448–4453.
   Google Scholar
• Sullivan SD, Moenter SM. Neurosteroids alter γ-aminobutyric acid postsynaptic currents in gonadotropin-releasing hormone neurons: a possible mechanism for direct steroidal control. Endocrinology 2003;144:4366–4375.
   PubMed Web of Science ®Google Scholar
• Yin C, Ishii H, Tanaka N, Sakuma Y, Kato M. Activation of A-type γ-amino butyric acid receptors excites gonadotropin-releasing hormone neurons isolated from adult rats. J Neuroendocrinol 2008;20:566–575.
   PubMed Web of Science ®Google Scholar
• Majewska MD, Harrison NL, Schwartz RD, Baker JL, Paul SM SM. Steroid hormone metabolites are barbiturate-like modulators of the GABA receptor. Science 1986;232:1004–1007.
   PubMed Web of Science ®Google Scholar
• Timby E, Balgard M, Nyberg S, Spigset O, Andersson A, Porankiewicz-Asplund J, Purdy RH, Zhu D, Backstrom T, Sundstrom-Poromaa I. Pharmacokinetic and behavioral effects of allopregnanolone in healthy women. Psychopharmacology (Berl) 2006;186:414–424.
   PubMed Web of Science ®Google Scholar
• Gee KW, Chang WC, Briton RE, McEwen BS. GABA-dependent modulation of the Cl-ionophore by steroids in rat brain. Eur J Pharmacol 1987;136:419–423.
   PubMed Web of Science ®Google Scholar
• Corpechot C, Young J, Calvel M, Wehrey C, Veltz JN, Touyer G, Mouren M, Prasad VV, Banner C, Sjovall J. Neurosteroids: 3α-hydroxy-5α-pregnan-20-one and its precursors in the brain, plasma, and steroidogenic glands of male and female rats. Endocrinology 1993;133:1003–1009.
   PubMed Web of Science ®Google Scholar
• Genazzani AR, Petraglia F, Bernardi F, Casarosa E, Salvestroni C, Tonetti A, Nappi RE, Luisi S, Palumbo M, Purdy RH, et al. Circulating levels of allopregnanolone in humans, gender, age, and endocrine influences. J Clin Endocrinol Metab 1998;83:2099–2103.
   PubMed Web of Science ®Google Scholar
• Parizek A, Hill M, Kancheva R, Havlikova H, Kancheva L, Cindr J, Paskova A, Pouzar V, Cerny I, Drbohlav P, et al. Neuroactive pregnanolone isomers during pregnancy. J Clin Endocrinol Metab 2005;90:395–403.
   PubMed Web of Science ®Google Scholar
• Ottander U, Poromaa IS, Bjurulf E, Skytt A, Backstrom T, Olofsson JI. Allopregnanolone and pregnanolone are produced by the human corpus luteum. Mol Cell Endocrinol 2005;239:37–44.
   PubMed Web of Science ®Google Scholar
• Purdy RH, Morrow AL, Moore PH Jr, Paul SM. Stress-induced elevations of γ-aminobutyric acid type A receptor-active steroids in the rat brain. Proc Natl Acad Sci USA 1991;88:4553–4557.
   PubMed Web of Science ®Google Scholar
• Droogleever Fortuyn Hal A, van Broekhoven F, Span PN, Backstrom T, Zitman FG, Verkes RJ. Effects of PhD examination stress on allopregnanolone and cortisol plasma levels and peripheral bensodiazepine receptor density. Psychoneuroendocrinology 2004;29:1341–1344.
   PubMed Web of Science ®Google Scholar
• Genazzani AR, Palumbo MA, de Micheroux AA, Artini PG, Criscuolo M, Ficarra G, Gou AL, Benelli A, Bertolini A, Petraglia F, et al. Evidence for a role for the neurosteroid allopregnanolone in the modulation of reproductive function in female rats. Eur J Endocrinol 1995;133:375–380.
   PubMed Web of Science ®Google Scholar
• Laconi MR,Cabrera RJ. Effect of centrally injected allopregnanolone on sexual receptivity, luteinizing hormone release, hypothalamic dopamine turnover, and release in female rats. Endocrine 2002;17:77–83.
   PubMed Web of Science ®Google Scholar
• Hagino N, Ramaley JA, Gorski RA. Inhibition of estrogen-induced precocious ovulation by pentobarbital in the rat. Endocrinology 1966;78:451–454.
   Google Scholar
• Hedstrom H, Bixo M, Nyberg S, Spigset O, Zingmark E, Backstrom T. Studies of pharmacokinetic and pharmacodynamic properties of isoallopregnanolone in healthy women. Psychopharmacology (Berl) 2009;203:85–98.
   PubMed Web of Science ®Google Scholar
• Turkmen S, Lundgren P, Birzniece V, Zingmark E, Backstrom T, Johansson IM. 3β-20β-dihydroxy-5α-pregnane (UC1011) antagonism of the GABA potentiation and the learning impairment induced in rats by allopregnanolone. Eur J Neurosci 2004;20:1604–1612.
   PubMed Web of Science ®Google Scholar
• Purdy RH, Moore PH Jr, Rao PN, Hagino N, Yamaguchi T, Schmidt P, Rubinow DR, Morrow AL, Paul SM. Radioimmunoassay of 3α-hydroxy-5α-pregnan-20-one in rat and human plasma. Steroids 1990;55:290–296.
   PubMed Web of Science ®Google Scholar
• Wang M, Seippel L, Purdy RH, Backstrom T. Relationship between symptom severity and steroid variation in women with premenstrual symdrome: study on serum pregnenolone, pregnenolone sulfate, 5α-pregnane-3,20-dione and 3α-hydroxy-5α-pregnan-20-one. J Clin Endocrinol Metab 1996;81:1076–1082.
   PubMed Web of Science ®Google Scholar
• Havlikova H, Hill M, Kancheva L, Vrbikova J, Pouzar V, Cerny I, Kancheva R, Starka L. Serum profiles of free and conjugated neuroactive pregnanolone isomers in nonpregnant women of fertile age. J Clin Endocrinol Metab 2006;91:3092–3099.
   PubMed Web of Science ®Google Scholar
• Hill M, Cibula D, Havlikova H, Kancheva L, Fait T, Kancheva R, Parizek A, Starka L. Circulating levels of pregnanolone isomers during the third trimester of human pregnancy. J Steroid Biochem Mol Biol 2007;105:166–175.
   PubMed Web of Science ®Google Scholar
• Hagino N. Effects of Nembutal on LH release in baboons. Horm Metab Res 1979;11:296–300.
   PubMed Web of Science ®Google Scholar
• Murphy LL, Mahesh VB. Selective release of lutheinizing hormone by 3α-hydroxy-5α-pregnan-20-one in immature ovarieectomized estrogen-primed rats. Biol Reprod 1984;30:795–803.
   PubMed Web of Science ®Google Scholar
• Brann DW, Putnam CD, Mahesh VB. Gamma-aminobutyric acidA receptors mediate 3α-hydroxy-5α-pregnan-20-one-induced gonadotropin secretion. Endocrinology 1990;126:1854–1859.
   PubMed Web of Science ®Google Scholar
• El-Etr M, Akwa Y, Fiddes RJ, Robel P, Baulieu EE. A progesterone metabolite stimulates the release of gonadotropin-releasing hormone from GT1-1 hypothalamic neurons via the γ-aminobutyric acid type A receptor. Proc Natl Acad Sci USA 1995;92:3769–3773.
   PubMed Web of Science ®Google Scholar
• Wiebe JP. Nongenomic actions of steroids on gonadotropin release. Rec Progr Horm Res 1997;52:71–101.
   PubMedGoogle Scholar
• Han SK, Abraham IM, Herbison AE. Effect of GABA on GnRH neurons switches from depolarization to hyperpolarization at puberty in the female mouse. Endocrinology 2002;143:1459–1466.
   Google Scholar
• Shen H, Gong QH, Aoki C, Yuan M, Ruderman Y, Dattilo M, Williams K, Smith SS. Reversal of neurosteroid effects at α4β2δ GABAA receptors triggers anxiety at puberty. Nat Neurosci 2007;10:469–477.
   PubMed Web of Science ®Google Scholar
• Andréen L, Sundstrom-Poromaa I, Bixo M, Nyberg S, Backstrom T. Allopregnanolone concentration and mood – a bimodal association in postmenopausal women treated with oral progesterone. Psychopharmacology 2006;187:209–221.
   PubMed Web of Science ®Google Scholar
• Genazzani AD, Luisi M, Malavasi B, Strucchi C, Luisi S, Casarosa E, Bernardi F, Genazzani AR, Petraglia F. Pulsatile secretory characteristics of allopregnanolone, a neuroactive steroid, during the menstrual cycle and in amenorrheic subjects. Eur J Endocrinol 2002;146:347–356.
   PubMed Web of Science ®Google Scholar
• Bernardi F, Hartmann B, Casarosa E, Luisi S, Stomati M, Fadalti M, Florio P, Santuz M, Luisi M, Petraglia F, et al. High levels of serum allopregnanolone in women with premature ovarian failure. Gynecol Endocrinol 1998;12:339–345.
   PubMed Web of Science ®Google Scholar
• Stromstedt M, Warner M, Bannor CD, MacDonald PC, Gustafsson JA. Role of brain cytocrome P450 in regulation of the level of anaesthetic steroids in the brain. Mol Pharmacol 1993;44:1077–1083.
   PubMed Web of Science ®Google Scholar
• Stromberg J, Haage D, Taube M, Backstrom T, Lundgren P. Neurosteroid modulation of allopregnanolone and GABA effects on the GABA-A receptor. Neuroscience 2006;142:73–81.
   Google Scholar
• Sundstrom I, Backstrom T. Endocrine response to pregnanolone. Gynecol Endocrinol 1999;13:352–360.
   PubMed Web of Science ®Google Scholar