Darren M. Roesch, PhD
Division of Endocrinology and Metabolism
Department of Medicine
350 Building D
4000 Reservoir Road, NW
Washington, DC 20057
Tel: 202 687-0453
Fax: 202 687-2040
Effects of gonadal steroids on the secretion and activity of adrenal steroids and the role of these effects in gender and age-related differences in responsiveness to stress, metabolic homeostasis, and cardiorenal function.
There are profound gender related differences in responsiveness to stress, metabolic homeostasis, and cardiorenal function. For example, women have a higher incidence of many emotional and other psychological disorders that are typically precipitated by stress, and the prevalence of obesity is higher in women in most developed countries. In contrast, men are at a greater risk for cardiovascular and renal disease than age-matched, premenopausal women. The adrenal steroids are important modulators of stress, metabolic homeostasis, and cardiorenal function. The adrenal cortex secretes two primary classes of steroids, the mineralocorticoids (primarily aldosterone) and the glucocorticoids (primarily corticosterone in the rat and cortisol in the human). Secretion of the aldosterone is regulated by the renin-angiotensin system, and the renin-angiotensin system is activated by cardiovascular signals such as hypovolemia, hypotension, and reduced renal sodium load.
The primary function of aldosterone is to maintain blood volume, and thus blood pressure, by retaining sodium in the kidney. However, recent evidence indicates that aldosterone also regulates blood pressure via direct effects in the heart, brain, and vasculature. Over-activation of the renin-angiotensin-aldosterone system is associated with hypertension and cardiovascular disease. Secretion of the glucocorticoids is regulated by the hypothalmic-pituitary-adrenal axis, and the hypothalamic-pituitary-adrenal axis is activated by stressors such as hypotension, hypoglycemia, and psychosocial stimuli. The purpose of the glucocorticoids is to aid in the termination of the stressful stimulus by maintaining cardiovascular function and providing energy substrate. Long-term elevations in glucocorticoids in combination with elevations in insulin promote an abdominal obesity that is associated with diabetes and cardiovascular disease. Ongoing research in this laboratory indicates that gonadal steroids (testosterone, estrogen, progesterone) have profound effects on both the secretion and activity of mineralocorticoids and glucocorticoids. The purpose of this research program is to determine the effects of gonadal steroids on mineralocorticoid and glucocorticoid secretion and activity and the role of these effects in gender and age-related differences in responsiveness to stress, metabolic homeostasis and cardiorenal function.
- Roesch DM, Keller-Wood M 1997 Progesterone rapidly reduces arterial pressure in ewes. Am J Physiol 272:H386-91
- Roesch DM, Keller-Wood M 1999 Differential effects of pregnancy on mineralocorticoid and glucocorticoid receptor availability and immunoreactivity in cortisol feedback sites. Neuroendocrinology 70:55-62
- Roesch DM, Tian Y, Verbalis JG, Sandberg K 2000 Rat model for investigating ACTH-independent angiotensin-induced aldosterone secretion. J Renin Angiotensin Aldosterone Syst 1:36-9
- Roesch DM, Tian Y, Zheng W, Shi M, Verbalis JG, Sandberg K 2000 Estradiol attenuates angiotensin-induced aldosterone secretion in ovariectomized rats. Endocrinology 141:4629-36