Calcitonin is a physiological inhibitor of prolactin secretion in ovariectomized female rats.

Abstract

Calcitonin (CT) inhibits secretion of PRL when administered intravenously in rats and humans. It also inhibits PRL release from cultured rat anterior pituitary (AP) cells. Recent evidence suggests that CT-like immunoreactive peptide is synthesized and released from the AP gland. However, its physiological role in the regulation of PRL secretion has not been understood. Present studies tested the role of endogenous pituitary CT (pit-CT) in the regulation of PRL secretion in vivo by passive immunization. In the first group of experiments, ovariectomized (ovx) adult female rats were administered either preimmune or anti-salmon CT (sCT) serum, and their serum PRL levels were analyzed at various time points up to 3 h. A second group of experiments examined the effects of anti-sCT serum and dopamine on PRL release from cultured rate AP cells. In the next group of experiments, the regional distribution of pit-CT secretion was examined in different sections of the AP gland. In the last set, CT-like activity of AP extract was tested in neonatal rat kidney cells, which respond to CT with an increase in cAMP accumulation. These experiments also tested whether anti-sCT serum reduces AP extract-induced increase in cAMP accumulation. The results suggest that anti-sCT serum dramatically increased serum PRL levels (by 5-fold) of ovx rats within 30 min of administration. The serum PRL levels declined gradually after the peak. However, a significant increase in serum PRL levels was maintained by the anti-sCT serum for the duration of the experiment. The anti-serum also induced a significant increase in PRL release from cultured AP cells when added to the presence or absence of dopamine. The distribution profile of pit-CT within the AP gland suggests that the release of pit-CT immunoreactivity was significantly greater in the inner sections, and anti-sCT serum also caused greater increase in PRL release in these sections. Finally, AP extract and sCT stimulated cAMP accumulation in neonatal rat kidney cells, and anti-sCT serum significantly reduced AP extract-induced cAMP accumulation. These results demonstrate that pit-CT is an important regulator of tonic PRL secretion in female rats and can potently inhibit PRL secretion even in the presence of dopamine.

Calcitonin increases invasiveness of prostate cancer cells: Role for cyclic AMP-dependent protein kinase A in calcitonin action

“…To examine the effect of deprivation of endogenously expressed CT on invasiveness of PC-3M cells, we immunoneutralized endogenously secreted CT with rabbit anti-CT serum, which we have shown to be effective in neutralizing CT in various in vitro and in vivo systems. 8,9,12,33,34 The results that anti-CT serum decreased the invasion of PC-3M cells in a dosedependent fashion supports the hypothesis that endogenous CT plays an important role in invasive behavior of these cells. Although stimulatory action of CT on PC-3M cells was similar to EGF, a known stimulator of this process, it was dose-dependent only up to 50 nM and then declined at greater concentrations.…”

Sustained activation of Erk1/2 MAPK and cell growth suppression by the insert-negative, but not the insert-positive isoform of the human calcitonin receptor

“…However, it is likely that the CT/CTR system has actions unrelated to calcium homeostasis and skeletal preservation since both CT and CTR are expressed in extraskeletal sites (Fischer et al 1981, Hilton et al 1998, Nicholson et al 1988. Examples of additional roles for CT are physiological inhibition of prolactin secretion in the anterior pituitary (Shah et al 1996) and evidence that CT promotes implantation and early differentiation of blastocysts in the pregnant uterus (Zhu et al 1998). In reconsidering the physiology of CT, it is necessary to understand the significance of the CTR isoforms that result from alternative splicing of the primary transcript, and that are expressed in a tissue-specific manner (Kuestner et al 1994).…”

Intrapituitary Regulatory System of Proliferation of Mammotrophs in the Pituitary Gland

“…Calcitonin receptors can also be detected in rat anterior pituitary glands (Sun et al, 2002). Calcitonin inhibits PRL secretion (Shah et al, 1988(Shah et al, , 1996, and the proliferation of mammotrophs (Shah et al, 1999). This inhibitory action of calcitonin on mammotroph proliferation was attenuated by the immunoneutralization of TGF-β1 with anti-TGF-β1 serum.…”