Calcitonin-Like Immunoreactivity in Rat and Human Pituitary Glands: Histochemical, in Vitro, and in Vivo Studies*

Abstract

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.

Calcitonin is expressed in gonadotropes of the anterior pituitary gland: its possible role in paracrine regulation of lactotrope function

“…Receptors recognizing salmon (S) CT have been detected in specific regions of rat brain and the anterior pituitary (AP) gland (Fischer et al 1981, Sexton et al 1993, Sheward et al 1994, and complementary (c) DNAs for two such receptors have been cloned from a rat brain cDNA library (Albrandt et al 1993). Supporting the physiological relevance of CT actions in the AP gland are the findings of the presence of SCTI and human (H) CTI in rat and human hypothalami and the pituitary glands by several investigators (Deftos et al 1978, Margules et al 1979, Cooper et al 1980, Fischer et al 1981, Flynn et al 1981, Balabanova et al 1985, Deftos 1987, Sexton & Hilton 1992, Shah et al 1993, Hilton et al 1998. The evidence for the synthesis and secretion of CT-like immunoreactive peptides by primary cultures of the rat AP gland has also been presented (Deftos 1987, Shah et al 1993.…”

Calcitonin: regional distribution of the hormone and its binding sites in the human brain and pituitary.

“…The origin of the CT-producing C cells in the neural crest (3) may suggest a possible function ofCT in the central nervous system. Indeed, immunoreactive CT has been demonstrated in the nervous system ofa primitive ascidian, the sea-squirt, primitive chordates, the lizard, and the pigeon, as well as in the pituitary and the adrenal gland (4)(5)(6)(7)(8)(9)(10)(11). Among human neural tissues, immunoreactive CT has been detected in the cerebrospinal fluid and in extracts of the hypothalamus, pheochromocytoma, and a mucosal neuroma (12)(13)(14)(15)(16).…”

Alternative RNA processing events in human calcitonin/calcitonin gene-related peptide gene expression.

“…The possible expression of the calcitonin gene in primate and human pituitary gland was analyzed in light of the previously ambiguous data in the rat. Although calcitonin immunoreactive material has been reported in the rat pituitary, the nature of the reactive material was uncertain (32)(33)(34)(35)(36), and calcitonin mRNA was not detected in the rat pituitary gland in RNA blotting analyses (4,32). More sensitive analyses with nuclease Sl-resistance procedures (3) did detect minimal amounts of CGRP mRNA in rat pituitaries (data not shown); however, the levels were so low that they could reflect either initial hypothalamic contamination of the collected pituitaries or the fact that the levels of calcitonin mRNA in pituitary are minimally above limits of detection by this method.…”