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Departments of Surgery (S.P., G.V.S., R.R.) and Physiology (J.C., C.V.S.), University of Kansas Medical Center, Kansas City, Kansas 66160; and Department of Pharmaceutical Sciences (J.C., Y.P.S., G.V.S.), Texas Tech University Health Sciences Center, Amarillo, Texas 79106
Address all correspondence and requests for reprints to: Girish V. Shah, Ph.D., Department of Pharmaceutical Sciences, Texas Tech University Health Sciences Center, 1300 South Coulter Drive, Amarillo, Texas 79106. E-mail: girish{at}cortex.ama.ttuhsc.edu
Previous studies have shown that CT-like immunoreactive peptide(s) (pit-CT) is synthesized by the anterior pituitary (AP) gland, and exogenously added salmon(s) CT inhibits PRL release and PRL gene transcription in cultured AP cells. Anti-sCT serum, which immunoreacts with pit-CT, stimulates PRL secretion, suggesting pit-CT is a physiologically relevant PRL-inhibiting hormone. Using proliferating cell nuclear antigen (PCNA) staining and 5-bromo-2'deoxyuridine (BrdU) incorporation into newly replicated DNA, the effect of calcitonin (CT) on cellular proliferation in the rat anterior pituitary gland (AP) was examined. CT significantly attenuated PCNA-immunopositive as well as BrdU-positive AP cell populations in dispersed rat AP cells.
A second series of experiments tested the effects of CT on AP cell proliferation in vivo. OVX + E2 rats were injected with 200 µg CT (iv), the rats killed at various time points, and the APs were processed for BrdU staining. CT inhibited BrdU incorporation at all time points up to 15 h after the injection, and this inhibitory effect was reversed at later time points. The effect of CT was concentration dependent, and a maximal inhibition was observed 10 h after the CT injection. Subsequent experiments identified CT-responsive AP cell populations using double immunofluorescence for BrdU and either PRL or FSH. The number of BrdU-labeled lactotropes in the AP gland declined by 74% in the CT-treated rats. Neutralization of endogenous pit-CT by passive immunization with anti-sCT serum caused a 2-fold increase in AP cell proliferation. These results suggest an important role for the endogenous pit-CT in regulation of lactotrope population of the AP gland.
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