PULSATILE LUTEINIZING-HORMONE SECRETION IN PATIENTS WITH ADDISONS-DISEASE - IMPACT OF GLUCOCORTICOID SUBSTITUTION

The physiological and pathophysiological role of cortisol in pulsatile LH release was investigated in 14 patients (5 men, 6 premenopausal wo men, and 3 postmenopausal women) with Addison's disease. The explicit effect of cortisol in relation to the effect of corticotropin-releasin g factor (CRF), ACTH, and opioids was ensured by hypo-, normo-, and hy percortisolism. Hypocortisolism was obtained by 24-h discontinuation o f hydrocortisone (HC) followed by 23-h saline infusion. Eucortisolism was secured by infusion of HC (0.5 mg/kg) over 23 h. Stress-appropriat e hypercortisolism was obtained by infusion of HC (2.0 mg/kg) over 23 h, preceded by treatment for 5 days with dexamethasone (1.5 mg/day). T o imitate the normal diurnal rhythm for serum cortisol, HC was infused in graduated doses. Blood sampling was performed every 10 min during the last 10 h of the study period, followed by a LH-releasing hormone test (5 mu g, iv) and a TRH test (10 mu g, iv). In pre-and postmenopau sal women, the mean LH level and the LH pulsatility pattern were simil ar on the 3 occasions. In contrast, the mean LH level in men was signi ficantly reduced during hypocortisolism compared to that during eucort isolism (3.26 +/- 0.68 vs. 4.49 +/- 0.83 U/I; P < 0.05, and was associ ated with a clear decrease in LH pulse amplitude (1.09 +/- 0.33 vs. 1. 96 +/- 0.53 U/L; P < 0.05). During high doses of glucocorticoids, the mean LH level in men was significantly lower than that during eucortis olism (3.81 +/- 0.88 vs. 4.49 +/- 0.83 U/L; P < 0.05). In both men and women, the mean PRL levels increased significantly (P < 0.05) during hypocortisolism, whereas high glucocorticoid doses suppressed the mean PRL level (P < 0.05). The LH and PRL responses to LH-releasing hormon e and TRH were, however, similar during low, medium, and high cortisol levels in both men and women. In conclusion, our data suggest that th e attenuation of pulsatile LH secretion in men during hypo- and hyperc ortisolism is due to variations in the hypothalamic opioid activity se condary to alterations in serum cortisol levels. A higher level of opi oid receptor activity in men than in low estrogen women may explain th e gender differences.