On the time course, generality, and regulation of plasma progesterone release in male rats by stress exposure

Although progesterone is most commonly regarded in terms of its role in the female estrous cycle, reproductive behavior, and pregnancy, progesterone is also a precursor to corticosterone (CORT) and is released from the adrenal glands of both sexes in response to stress. However, the relationship between plasma CORT and progesterone during times of stress has not been well established. To better characterize dynamic changes in progesterone release as a result of stressor exposure, plasma progesterone levels were measured using enzyme immunoassay under multiple conditions, including after stress exposure (footshock, restraint, and forced swim), manipulations of the hypothalamic-pituitaryadrenal axis (injection of metyrapone or dexamethasone, or adrenalectomy), and in response to CRH and ACTH injections. When plasma levels of ACTH, CORT, and progesterone were analyzed across studies, CORT and progesterone were found to be highly correlated and rarely dissociated. Additionally, it appears that in male rats, the adrenal glands are the principle source of circulating progesterone in response to stress. Interestingly, a detailed time course indicated lack of a circadian rhythm of progesterone secretion, despite a robust rhythm of circulating CORT. The current studies provide critical new information on the coincident release of progesterone and CORT in response to stress and their somewhat paradoxical dissociation across the circadian rhythm. These findings provide an important foundation for future studies that will examine the role of stress-induced progesterone in behavioral, neuroimmune, and neuroendocrine responses to stress.