Genazzani A R, Petraglia F, Bernardi F, Casarosa E, Salvestroni C, Tonetti A, Nappi R E, Luisi S, Palumbo M, Purdy R H, Luisi M
Department of Reproductive Medicine and Child Development, University of Pisa, Italy.
J Clin Endocrinol Metab. 1998 Jun;83(6):2099-103. doi: 10.1210/jcem.83.6.4905.
Allopregnanolone is a neuroactive steroid involved in modulating behavioral functions, stress, and neuroendocrine axes in rats. Changes in plasma allopregnanolone levels throughout the menstrual cycle have been reported in healthy women, but there exists no information on the possible gender or age-related changes or on the source(s) of circulating allopregnanolone. The aim of the present study was to assess serum allopregnanolone concentrations according to gender, menstrual cycle, age, and menopause in normal men and women; serum progesterone (P) and dehydroepiandrosterone (DHEA) levels were evaluated in the same specimens. In addition, the possible source of circulating allopregnanolone in fertile women was investigated by using stimulatory and inhibitory endocrine 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 specific RIAs. Allopregnanolone levels in fertile women in the follicular phase were similar to those in age-matched men; no significant difference was found between fertile women in the follicular phase and postmenopausal 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 higher in women than in men and were higher in fertile women than in postmenopausal women (P < 0.01). Both P and DHEA showed an age-related decrease in men and women (P < 0.01). Serum allopregnanolone and P, but not DHEA, significantly increased in response to a GnRH test, whereas corticotropin-releasing factor and ACTH tests elicited a significant increase in allopregnanolone, P, and DHEA levels (P < 0.01). The suppression 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 decrease, serum allopregnanolone levels in women do not change with age and correlate with P levels during the menstrual cycle and in response to endocrine tests. Ovary and adrenal cortex may be major sources of circulating allopregnanolone in fertile women.
别孕烯醇酮是一种具有神经活性的类固醇，参与调节大鼠的行为功能、应激反应及神经内分泌轴。已有报道称健康女性在整个月经周期中血浆别孕烯醇酮水平会发生变化，但关于其可能存在的性别或年龄相关变化以及循环别孕烯醇酮的来源尚无相关信息。本研究的目的是评估正常男性和女性血清中别孕烯醇酮的浓度，并根据性别、月经周期、年龄和绝经状态进行分析；同时对相同样本中的血清孕酮（P）和脱氢表雄酮（DHEA）水平进行评估。此外，通过对卵巢和/或肾上腺皮质进行刺激和抑制内分泌试验，研究育龄女性循环别孕烯醇酮的可能来源。本研究纳入了189名育龄女性、112名绝经后女性和46名男性。血清类固醇水平在提取后使用特异性放射免疫分析法进行测定。育龄女性卵泡期的别孕烯醇酮水平与年龄匹配的男性相似；卵泡期育龄女性与绝经后女性之间未发现显著差异。黄体期育龄女性的别孕烯醇酮水平最高（P < 0.01）。男性中观察到与年龄相关的下降（P < 0.01），而女性中未观察到。女性的P和DHEA水平显著高于男性，且育龄女性高于绝经后女性（P < 0.01）。男性和女性的P和DHEA均呈现与年龄相关的下降（P < 0.01）。促性腺激素释放激素（GnRH）试验后，血清别孕烯醇酮和P显著升高，但DHEA未升高，而促肾上腺皮质激素释放因子（CRF）和促肾上腺皮质激素（ACTH）试验可使别孕烯醇酮、P和DHEA水平显著升高（P < 0.01）。地塞米松抑制肾上腺类固醇生成可显著降低别孕烯醇酮和DHEA的血清水平（P < 0.01）。总之，本研究表明，尽管男性呈现与年龄相关的下降，但女性血清别孕烯醇酮水平不随年龄变化，且与月经周期及内分泌试验中的P水平相关。卵巢和肾上腺皮质可能是育龄女性循环别孕烯醇酮的主要来源。
