CIRCULATING LEVELS OF ALLOPREGNANOLONE IN HUMANS - GENDER, AGE, AND ENDOCRINE INFLUENCES

Allopregnanolone is a neuroactive steroid involved in modulating behav ioral functions, stress, and neuroendocrine axes in rats. Changes in p lasma allopregnanolone levels throughout the menstrual cycle have been reported in healthy women, but there exists no information on the pos sible gender or age-related changes or on the source(s) of circulating allopregnanolone. The aim of the present study was to assess serum al lopregnanolone concentrations according to gender, menstrual cycle, ag e, and menopause in normal men and women; serum progesterone (P) and d ehydroepiandrosterone (DHEA) levels were evaluated in the same specime ns. In addition, the possible source of circulating allopregnanolone i n fertile women was investigated by using stimulatory and inhibitory e ndocrine tests acting on the ovary and/or adrenal cortex. The present study included 189 fertile women, 112 postmenopausal women, and 46 men . Serum steroid levels were determined after extraction, using specifi c RIAs. Allopregnanolone levels in fertile women in the follicular pha se were similar to those in age-matched men; no significant difference was found between fertile women in the follicular phase and postmenop ausal women. The highest levels were found in fertile women during the luteal phase (P < 0.01). An age-related decrease was observed in men (P < 0.01), but not in women. P and DHEA levels were significantly hig her in women than in men and were higher in fertile women than in post menopausal women (P < 0.01). Both P and DHEA showed an age-related dec rease in men and women (P < 0.01). Serum allopregnanolone and P, but n ot DHEA, significantly increased in response to a GnRH test, whereas c orticotropin-releasing factor and ACTH tests elicited a significant in crease in allopregnanolone, P, and DHEA levels (P < 0.01). The suppres sion of adrenal steroidogenesis by dexamethasone markedly reduced both allopregnanolone and DHEA serum levels (P < 0.01). In conclusion, the present study demonstrated that although men show an age-related decr ease, serum allopregnanolone levels in women do not change with age an d correlate with P levels during the menstrual cycle and in response t o endocrine tests. Ovary and adrenal cortex may be major sources of ci rculating allopregnanolone in fertile women.