Chronic Administration of Corticotropin-Releasing Factor Increases Pituitary Corticotroph Number*

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Abstract
The effect of chronic administration of CRF on rat pituitary morphology was studied. Experimental animals received CRF(10 .mu.g/day) over a period of 52 days by means of sc osmotic pumps changed at 10- to 14-day intervals. The average 0800 h plasma corticosterone levels in the treated animals were significantly greater than control values [7.52 .+-. 0.99 (.+-. SE) vs. 1.14 .+-. 0.5 .mu.g/dl; P < 0.001]. The CRF-treated animals also had a significant greater adrenal weight (16.44 .+-. 1.38 vs. 12.24 .+-. 0.85 mg; P < 0.05) and lower thymus weight (164 .+-. 12 vs. 248 .+-. 27 mg; P < 0.005). There was a marked increase in the number of ACTH-producing cells in the anterior pituitaries of the rats that received CRF (13.3 .+-. 0.8% vs. 4.5 .+-. 0.3% ACTH-producing cells; P < 0.001), as determined by immunocytochemical methods. Corticotrophs of rats treated with CRF manifested a significant incrase in nuclear area (24.0 .+-. 0.7 vs. 21.4 .+-. 0.4 .mu.m2; P < 0.001) and an increased diameter of forming and storage granules (191.1 .+-. 1.1 vs. 158.6 .+-. 3.5 nm and 196.1 .+-. 1.2 vs. 170.1 .+-. 3.7 nm, respectively; P < 0.001). There was no demonstrable increase in ACTH cell area. These data indicate that long term administration of CRF is capable of increasing the number of pituitary corticotrophs. It also supports the view that the corticotroph hyperplasia occurring after adrenalectomy, in unusual cases of ectopic CRF production, and in rare instances of Cushing''s disease is a proliferative response to CRF.