Calcitonin-like immunoreactivity in rat and human pituitary glands: histochemical, in vitro, and in vivo studies.
This study was designed to determine whether pituitary glands contain an immunoreactive material which reacts with antisera to calcitonin (CT) and, if so, whether secretion of the material could be demonstrated. Testing 15 antisera to rat and human CT and using an immunoperoxidase method, we found 2 antisera to human CT which stained rat pituitaries and several which stained human pituitaries. Essentially all cells in the rat intermediate lobe and scattered cells in the rat and human anterior lobes showed staining, and staining was not entirely abolished by prior adsorption of antisera with rat or human CT. The 2 antisera which stained rat pituitaries showed cross-reactivity with several synthetic human CT fragments (1-18, 11-23 and 22-32) but not with ACTH-(1-39), ACTH-(1-24), beta-endorphin, alpha- or beta MSH, or bovine lipotropin. Crude extracts of pituitaries from 2 strains of young rats showed CT-like immunoreactivity which could be measured easily by RIA (0.2-0.3 ng/gland). In vivo, an antiserum which stained pituitaries and 1 which did not were compared using young rats made hypercalcemic (15-20 mg/dl) with iv Ca. In rats with thyroids, both antisera showed an increase in serum CT of more than 15-fold whether the pituitary was present or absent. In thyroidectomized rats, serum CT remained undetectable (less than 50 to 100 pg/ml) during hypercalcemia even if the pituitary was present. In vitro, rat pituitaries in a serum-free medium did not release measurable amounts of immunoreactive CT-like material even when medium contained high Ca (2.5 mM), high K (25 mM), or TRH (10(-6) M). Therefore, the findings agree with other reports of a CT-like material in the pituitary, but no secretion of the material could be demonstrated. We hypothesize that the material is not authentic CT but is, rather a related peptide sequence probably contained in the 31 K precursor protein of ACTH-beta-lipotropin.