No abstract

CRF, from the paraventricular nucleus of the hypothalamus (PVN), is the major hypothalamic releasing factor that controls pituitary ACTH. Recently, the mRNA for CRF and the CRF peptide have been detected in other brain sites. However, there is little information on the function and regulation of CRF in brain sites outside the paraventricular nucleus. We investigated the content of CRF mRNA in the PVN, the central nucleus of the amygdala (CN), the bed nucleus of the stria terminalis (BN), and the supraoptic nucleus (SON). Northern gel analysis showed that the mRNA for CRF is present in the BN, CN, and SON as well as the PVN, and that all are the same size. In response to adrenalectomy, the level of hybridizable mRNA increased 2.75-fold over 7 days in the PVN; there was no change in the CN, BN, or SON. High dose dexamethasone decreased, but did not eliminate, the PVN CRF mRNA; it was without effect in the other sites. Glucocorticoid replacement with constant low blood levels of corticosterone (5.6 +/- 0.3 micrograms/100 ml) suppressed plasma ACTH and decreased thymus weight while reducing, but not eliminating, PVN CRF mRNA. We conclude that the same sized mRNA for CRF is synthesized in the PVN, BN, CN, and SON, but only the PVN mRNA responds to alterations of peripheral glucocorticoid status. This may imply that only CRF from the PVN is involved in control of the hypothalamic-pituitary-adrenal axis.

We describe a middle-aged man with late-onset multiple sclerosis and an incidentally discovered asymptomatic adrenal mass. He had no symptoms or signs of hypercortisolism. A 24-h profile revealed fluctuating serum cortisol values (between 15.1 and 4.7 micrograms/dl) and inappropriately low plasma ACTH values. Urinary cortisol excretion was 89 and 106 micrograms/day on two occasions. After a 4-h ACTH infusion, serum cortisol rose from 6.3 to 108 micrograms/dl. The serum dehydroepiandrosterone level, 33 ng/dl before ACTH stimulation, did not change. During dexamethasone administration, the lowest daily urinary cortisol excretion was 37 micrograms/day, and 17-ketosteroid excretion was 8 mg/day. The response to metyrapone showed a rise of serum 11-deoxycortisol to 25.6 micrograms/dl and of ACTH to 169.5 pg/ml. After removal of the tumor, most likely an adenoma, the circadian pattern of cortisol and ACTH was normal. During a 4-h ACTH infusion, the serum cortisol level rose from 10 to 27 micrograms/dl, and dehydroepiandrosterone rose from 62 to 90 ng/dl. During dexamethasone administration, daily urinary cortisol excretion decreased to 12 micrograms/day, and 17-ketosteroid excretion dropped to 3.9 mg/day. These data show that while the tumor appeared clinically to be nonfunctional, it was producing cortisol and possibly androgens autonomously, albeit at levels too low to cause complete suppression of the pituitary-adrenal axis.

No abstract