Glucocorticoids, stress, and fertility.
Modifications of the hypothalamo-pituitary-adrenal axis and associated changes in circulating levels of glucocorticoids form a key component of the response of an organism to stressful challenges. Increased levels of glucocorticoids promote gluconeogenesis, mobilization of amino acids, and stimulation of fat breakdown to maintain circulating levels of glucose necessary to mount a stress response. In addition to profound changes in the physiology and function of multiple tissues, stress and elevated glucocorticoids can also inhibit reproduction, a logical effect for the survival of self. Precise levels of glucocorticoids are required for proper gonadal function; where the balance is disrupted, so is fertility. Glucocorticoids affect gonadal function at multiple levels in hypothalamo-pituitary-gonadal axis: 1) the hypothalamus (to decrease the synthesis and release of gonadotropin-releasing hormone [GnRH]); 2) the pituitary gland (to inhibit the synthesis and release of luteinizing hormone [LH] and follicle stimulating hormone [FSH]); 3) the testis/ovary (to modulate steroidogenesis and/or gametogenesis directly). Furthermore, maternal exposure to prenatal stress or exogenous glucocorticoids can lead to permanent modification of hypothalamo-pituitary-adrenal function and stress-related behaviors in offspring. Glucocorticoids are vital to many aspects of normal brain development, but fetal exposure to superabundant glucocorticoids can result in life-long effects on neuroendocrine function. This review focuses on the molecular mechanisms believed to mediate glucocorticoid inhibition of reproductive functions and the anatomical sites at which these effects take place.
Whirledge
S
S
Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, National Institutes of Health/DHHS, Research Triangle Park, Durham, NC 27709, USA.
Cidlowski
J A
JA
D005260:Female; D005298:Fertility; D005640:Follicle Stimulating Hormone / Q000096:biosynthesis; D005938:Glucocorticoids / Q000009:adverse effects / Q000378:metabolism*; D007987:Gonadotropin-Releasing Hormone / Q000096:biosynthesis; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism*; D008297:Male; D010053:Ovary / Q000378:metabolism; D010913:Pituitary-Adrenal System / Q000378:metabolism*; D011247:Pregnancy; D013312:Stress, Physiological; D013315:Stress, Psychological / Q000378:metabolism*; D013737:Testis / Q000378:metabolism
D005938:Glucocorticoids; D007987:Gonadotropin-Releasing Hormone; D005640:Follicle Stimulating Hormone