A Glucocorticoid Sensitive Biphasic Rhythm of Testosterone Secretion

Abstract

Studies of the hypothalamic-pituitary-adrenal (HPA) axis and the hypothalamic-pituitary-testicular (HPT) axis have revealed a reciprocal relationship between these two endocrine pathways. In rats, for example, disruption of the HPT axis alters the circadian secretion of corticosterone. Stress, on the other hand, can have varying effects on testosterone secretion in both rats and humans. Furthermore, in contrast to humans, where several pulses of testosterone secretion can be detected across the 24-h period with the largest in the morning, rats appear to exhibit a diurnal rhythm of testosterone secretion. In the present study, we used an automated blood sampling system to investigate the true circadian pattern of testosterone secretion under basal conditions and investigated how this responds to changes in levels of circulating corticosteroids. Analysis of plasma testosterone revealed the expected bimodal pattern of basal testosterone secretion. The two secretory episodes were 12.59 h +/- 41 min apart and 4.04 h +/- 16 min long, with one in the light phase and the other in the dark phase of the cycle. Interestingly, when both testosterone and corticosterone diurnal profile were compared, we found that the circadian rise in plasma corticosterone levels falls neatly between the two testosterone secretory episodes. Treatment of rats with the synthetic glucocorticoid methylprednisolone in their drinking water abolished the normal bimodal profile of testosterone secretion. These rats show transient pulses of testosterone throughout the 24 h, but no circadian pattern. By contrast, adrenalectomised rats maintain their bimodal circadian pattern, suggesting that an intact HPA axis is not necessary for generation of the endogenous HPT rhythm. Thus, although the circadian rhythm of testosterone does not depend on normal HPA function, increased levels of glucocorticoids can abolish normal HPT rhythmicity.