Chrousos G P, Torpy D J, Gold P W
Ann Intern Med. 1998 Aug 1;129(3):229-40. doi: 10.7326/0003-4819-129-3-199808010-00012.
The hypothalamic-pituitary-adrenal axis exerts profound, multilevel inhibitory effects on the female reproductive system. Corticotropin-releasing hormone (CRH) and CRH-induced proopiomelanocortin peptides inhibit hypothalamic gonadotropin-releasing hormone secretion, whereas glucocorticoids suppress pituitary luteinizing hormone and ovarian estrogen and progesterone secretion and render target tissues resistant to estradiol. The hypothalamic-pituitary-adrenal axis is thus responsible for the "hypothalamic" amenorrhea of stress, which is also seen in melancholic depression, malnutrition, eating disorders, chronic active alcoholism, chronic excessive exercise, and the hypogonadism of the Cushing syndrome. Conversely, estrogen directly stimulates the CRH gene promoter and the central noradrenergic system, which may explain adult women's slight hypercortisolism; preponderance of affective, anxiety, and eating disorders; and mood cycles and vulnerability to autoimmune and inflammatory disease, both of which follow estradiol fluctuations. Several components of the hypothalamic-pituitary-adrenal axis and their receptors are present in reproductive tissues as autacoid regulators. These include ovarian and endometrial CRH, which may participate in the inflammatory processes of the ovary (ovulation and luteolysis) and endometrium (blastocyst implantation and menstruation), and placental CRH, which may participate in the physiology of pregnancy and the timing of labor and delivery. The hypercortisolism of the latter half of pregnancy can be explained by high levels of placental CRH in plasma. This hypercortisolism causes a transient postpartum adrenal suppression that, together with estrogen withdrawal, may partly explain the depression and autoimmune phenomena of the postpartum period.
下丘脑 - 垂体 - 肾上腺轴对女性生殖系统具有深刻的、多层次的抑制作用。促肾上腺皮质激素释放激素（CRH）以及CRH诱导的阿黑皮素原肽会抑制下丘脑促性腺激素释放激素的分泌，而糖皮质激素则会抑制垂体促黄体生成素以及卵巢雌激素和孕激素的分泌，并使靶组织对雌二醇产生抵抗。因此，下丘脑 - 垂体 - 肾上腺轴导致了应激性“下丘脑性”闭经，这种闭经在忧郁症、营养不良、饮食失调、慢性酒精中毒、长期过度运动以及库欣综合征所致的性腺功能减退中也可见到。相反，雌激素会直接刺激CRH基因启动子以及中枢去甲肾上腺素能系统，这或许可以解释成年女性轻微的皮质醇增多症、情感障碍、焦虑症和饮食失调的高发率，以及情绪周期和对自身免疫性疾病及炎症性疾病的易感性，而这两者均与雌二醇波动有关。下丘脑 - 垂体 - 肾上腺轴的几个组成部分及其受体作为自分泌调节因子存在于生殖组织中。这些包括卵巢和子宫内膜CRH，它们可能参与卵巢（排卵和黄体溶解）和子宫内膜（胚泡着床和月经）的炎症过程，以及胎盘CRH，它可能参与妊娠生理以及分娩的时间调控。妊娠后半期的皮质醇增多症可由血浆中高水平的胎盘CRH来解释。这种皮质醇增多症会导致产后肾上腺功能的短暂抑制，这与雌激素撤退一起，可能部分解释了产后的抑郁和自身免疫现象。
