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

Ren, Yuan; Chien, Jeremy; Sun, Yi‐Min; Shah, Girish V.

doi:10.1677/joe.0.1710217

Cited by 29 publications

(23 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…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.…”

Section: Discussionsupporting

confidence: 68%

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

et al. 2005

View full text Add to dashboard Cite

Calcitonin (CT) is synthesized and secreted in prostate epithelium, and its secretion from malignant prostates is several-fold higher than from benign prostates. CT receptor (CTR) is expressed in malignant prostate epithelium, and its activation stimulates growth of prostate cancer (PC) cells via activation of adenylyl cyclase and calcium/phospholipid pathways. To identify the role of ''CT System'' in prostate cancer, we tested the expression of CT and CTR mRNAs in invading tumor cells of prostate cancer specimens. The effect of CT on in vitro invasion of PC cell lines and on activation of gelatinases was also examined. The cells of primary tumors and those invading stroma co-expressed CT/CTR mRNAs. Exogenously added CT increased in vitro invasion of PC cell lines and caused a rapid, several-fold but transient increase in protein kinase A activity. In contrast, anti-CT serum caused a dose-dependent inhibition of in vitro invasion of PC-3M cells. CT also increased the concentration and activities of MMP-2 and MMP-9. Rp.cAMP, a competitive inhibitor of cAMP-dependent protein kinase A, myristoylated protein kinase A inhibitory peptide (PKI) as well as the expression of dominant negative form of PKA all attenuated basal in vitro invasion of PC-3M cells, and CT could not increase in vitro invasiveness in their presence. These results suggest that overexpression of ''CT System'' in invasive PC tumors significantly contributes to increased invasiveness of prostate cancer cells. The action of CT may be mediated by protein kinase A signaling, which subsequently leads to increased cell invasion and secretion of gelatinases. ' 2005 Wiley-Liss, Inc.Key words: prostate cancer; invasion; calcitonin; PKA; metastasis Calcitonin (CT), a 32 amino acid peptide produced by C cells of mammalian thyroid, has also been detected in human brain, the pituitary gland, lung carcinoma as well as the conditioned media from the cultures of primary prostate epithelial cells.1-6 Although most well-known functions of CT include inhibition of bone resorption, renal regulation of sodium, phosphate, calcium and neuromodulation, 6 CT has also been shown to regulate secretory and proliferative functions of several organs. [7][8][9] Previous studies from this laboratory have shown that immunoreactive CT (iCT) is secreted by primary prostate epithelial cells, and its secretion from cancer-derived primary prostate cells is several-fold higher than that from the cells of benign prostatic hyperplasia origin. 1 We have reported that mRNAs for CT and its receptor (CTR) are selectively localized to the basal epithelium of benign prostates but are distributed throughout the epithelium of malignant prostates. High-affinity CT receptors have been identified in membrane preparations of primary tumors as well as androgen-responsive LNCaP and highly metastatic but androgen refractory PC-3M prostate cancer cells.10 Exogenously added CT stimulates the proliferation of LNCaP cells by stimulating cAMP accumulation and increasing cytoplasmic Ca 21 transients, and CT al...

show abstract

Section: Discussionsupporting

confidence: 68%

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

et al. 2005

View full text Add to dashboard Cite

show abstract

“…It has also been implicated in the regulation of several functions in reproductive and neuroendocrine tissues (31)(32)(33)(34)(35).…”

Section: Discussionmentioning

confidence: 99%

Calcitonin Stimulates Multiple Stages of Angiogenesis by Directly Acting on Endothelial Cells

et al. 2005

View full text Add to dashboard Cite

Although a strong correlation between neuroendocrine differentiation and angiogenesis of prostate cancer has been reported, no mechanistic link between the two events has been established. Because neuropeptide calcitonin is secreted by prostate tumors and endothelial cells are known to express calcitonin receptor-like receptor, we examined the potential action of calcitonin on endothelial cells. The presence of calcitonin receptor, calcitonin receptor-like receptor, and receptor activity-modifying proteins in human microvessel endothelial-1 cells was tested by reverse transcriptase-PCR (RT-PCR). The proangiogenic action of calcitonin was examined in several in vitro models of angiogenesis using HMEC-1 cells and also in vivo using dorsal skinfold assays. Calcitonin expression of PC-3M cells was modulated, and its effect on angiogenesis was examined in in vitro as well as in vivo models. The results of RT-PCR and radioligand receptor assays showed the presence of functional calcitonin receptor in HMEC-1 cells. Calcitonin stimulated all phases of angiogenesis through the calcitonin receptor, but its effect on tube morphogenesis by endothelial cells occurred at the concentration of the K d of calcitonin receptor. Silencing of calcitonin receptor expression in HMEC-1 cells abolished calcitonin-induced tube formation. Vascular endothelial growth factor antibodies attenuated but did not abolish calcitonin-induced tube morphogenesis. PC-3M prostate cancer cells induced angiogenesis in in vivo and in vitro models. Overexpression of calcitonin in PC-3M cells increased their angiogenic activity, whereas the silencing of calcitonin expression abolished it. These results show that prostate tumor-derived calcitonin may play an important role in prostate tumor growth by regulating intratumoral vascularization. (Cancer Res 2005; 65(18): 8519-29)

show abstract

“…That CT could act as a paracrine mediator in such a dialog is supported by the fact that: (i) uterine CT was shown to exert its effects through a paracrine circuit during murine embryo implantation, with maternally derived CT and embryo-derived CTR making up this circuit (Wang et al 1998); (ii) in the anterior pituitary gland, CT acts as a paracrine signaling pathway between the gonadotrope and lactotrope cell types to suppress prolactin secretion (Ren et al 2001); (iii) the closely related PTHrP also makes up a paracrine signaling pathway that is indispensable for early mammary development (Wysolmerski et al 1995); and (iv) progesterone -an upstream affecter of CT expression Figure 5 Immunohistochemistry reveals CTR expression is limited to the myoepithelial cell lineage (black arrow) of the mammary gland of the 12-week-old virgin (A) and mid-pregnant mouse (B); unlike CT, CTR is not expressed in the luminal epithelial compartment (red arrow). Higher magnifications of (A) and (B) are shown in (C) and (D) respectively.…”

Section: Discussionmentioning

confidence: 99%

Progesterone induction of calcitonin expression in the murine mammary gland

Ismail

DeMayo

Amato

et al. 2004

Journal of Endocrinology

View full text Add to dashboard Cite

Progesterone, via its nuclear receptor, is mandatory not only for the induction and specification of mammary gland ductal side-branching and lobuloalveologenesis but also for carcinogen-induced mammary tumorigenesis. Notwithstanding these recent advances, a more comprehensive molecular explanation of progesterone-induced mammary morphogenesis is contingent upon the identification and characterization of mammary molecular targets that are responsive to the progesterone signal. Toward this goal, we report that calcitonin, a 32 amino acid peptide hormone involved in calcium homeostasis, is exclusively expressed in, and secreted from, luminal epithelial cells within the mammary gland of the pregnant mouse, and, importantly, its expression is progesterone-dependent. Conversely, the calcitonin receptor is present during all stages of post-natal mammary development examined, is localized to the myoepithelial cell lineage, and is not regulated by progesterone. Because calcitonin induction spatiotemporally correlates with increases in progesterone-induced mammary gland proliferation and structural remodeling, we posit that calcitonin -through its receptor -may be involved in one or both of these progesterone-dependent processes.

show abstract

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

Cited by 29 publications

References 54 publications

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

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

Calcitonin Stimulates Multiple Stages of Angiogenesis by Directly Acting on Endothelial Cells

Progesterone induction of calcitonin expression in the murine mammary gland

Contact Info

Product

Resources

About