Cortisol, parathyroid hormone-related protein and the onset of calcium secretion by the mammary gland of the goat

1997 ◽  
Vol 64 (4) ◽  
pp. 633-636
Author(s):  
GORDON E. THOMPSON ◽  
S. KHAWAR ABBAS ◽  
CARL HOLT ◽  
ANTHONY D. CARE
Keyword(s):  
Mammary Gland ◽  
Parathyroid Hormone ◽  
Epithelial Cells ◽  
Tight Junctions ◽  
Calcium Transport ◽  
Extracellular Fluid ◽  
Secretory Cells ◽  
Related Protein ◽  
Parathyroid Hormone Related Protein ◽  
Calcium Secretion

During lactogenesis in the goat, the onset of secretion of calcium into milk occurs at parturition (Thompson et al. 1995) at approximately the same time as the onset of secretion of parathyroid hormone-related protein (PTHrP) by the mammary gland (Ratcliffe et al. 1992); these events may be unrelated or PTHrP may be involved in calcium transport from blood to milk.Parturition in goats is initiated by fetal secretion of cortisol (Flint et al. 1978) and maternal secretion of cortisol also increases (Paterson & Linzell, 1971). Injecting cortisol locally into the sinus of a mammary gland of the late-pregnant goat when the tight junctions between secretory epithelial cells appear to be ‘loose’, and injectate can reach the basolateral surfaces of secretory cells, stimulates an early tightening of these junctions (Thompson, 1996) as occurs naturally at parturition. This tightening can be produced by an increased concentration of ionized calcium in the extracellular fluid of the gland (Neville & Peaker, 1981).The experiments reported here were undertaken to determine if cortisol injection stimulates the mammary gland to secrete both PTHrP and calcium before parturition.

Rescue of the parathyroid hormone-related protein knockout mouse demonstrates that parathyroid hormone-related protein is essential for mammary gland development

Development ◽  
1998 ◽  
Vol 125 (7) ◽  
pp. 1285-1294 ◽  
Author(s):  
J.J. Wysolmerski ◽  
W.M. Philbrick ◽  
M.E. Dunbar ◽  
B. Lanske ◽  
H. Kronenberg ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Parathyroid Hormone ◽  
Epithelial Cells ◽  
Mammary Epithelial Cells ◽  
Branching Morphogenesis ◽  
Mammary Epithelial ◽  
Related Protein ◽  
Transgenic Expression ◽  
Parathyroid Hormone Related Protein ◽  
Pthrp Receptor

Parathyroid hormone-related protein (PTHrP) was originally discovered as a tumor product that causes humoral hypercalcemia of malignancy. PTHrP is now known to be widely expressed in normal tissues and growing evidence suggests that it is an important developmental regulatory molecule. We had previously reported that overexpression of PTHrP in the mammary glands of transgenic mice impaired branching morphogenesis during sexual maturity and early pregnancy. We now demonstrate that PTHrP plays a critical role in the epithelial-mesenchymal communications that guide the initial round of branching morphogenesis that occurs during the embryonic development of the mammary gland. We have rescued the PTHrP-knockout mice from neonatal death by transgenic expression of PTHrP targeted to chondrocytes. These rescued mice are devoid of mammary epithelial ducts. We show that disruption of the PTHrP gene leads to a failure of the initial round of branching growth that is responsible for transforming the mammary bud into the rudimentary mammary duct system. In the absence of PTHrP, the mammary epithelial cells degenerate and disappear. The ability of PTHrP to support embryonic mammary development is a function of amino-terminal PTHrP, acting via the PTH/PTHrP receptor, for ablation of the PTH/PTHrP receptor gene recapitulates the phenotype of PTHrP gene ablation. We have localized PTHrP expression to the embryonic mammary epithelial cells and PTH/PTHrP receptor expression to the mammary mesenchyme using in situ hybridization histochemistry. Finally, we have rescued mammary gland development in PTHrP-null animals by transgenic expression of PTHrP in embryonic mammary epithelial cells. We conclude that PTHrP is a critical epithelial signal received by the mammary mesenchyme and involved in supporting the initiation of branching morphogenesis.

Production of parathyroid hormone-related protein by the rat mammary gland in pregnancy and lactation

1992 ◽  
Vol 263 (6) ◽  
pp. E1077-E1085 ◽  
Author(s):  
M. Rakopoulos ◽  
S. J. Vargas ◽  
M. T. Gillespie ◽  
P. W. Ho ◽  
H. Diefenbach-Jagger ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Parathyroid Hormone ◽  
Mammary Tissue ◽  
Secretory Cells ◽  
Related Protein ◽  
Sprague Dawley ◽  
Parathyroid Hormone Related Protein ◽  
Pregnancy And Lactation ◽  
Rat Mammary Gland ◽  
In Pregnancy

Production of parathyroid hormone-related protein by the rat mammary gland in pregnancy and lactation. Am. J. Physiol. 263 (Endocrinol. Metab. 26): E1077-E1085, 1992.--Production of parathyroid hormone-related protein (PTHrP) by the mammary gland of Sprague-Dawley rats has been examined using immunohistochemistry and in situ hybridization to detect PTHrP and PTHrP mRNA, respectively. PTHrP and PTHrP mRNA could be demonstrated in nests of epithelial cells of the developing mammary gland at day 14 of pregnancy and in the epithelial secretory cells lining the alveoli during the latter stages of pregnancy and during lactation. A specific radioimmunoassay was also used to measure the concentration of PTHrP secreted in the milk throughout lactation. The concentration of PTHrP in milk was relatively low initially but increased during the latter stages of lactation, whereas calcium concentrations remained virtually constant throughout lactation. No correlation was found between the concentrations of calcium and PTHrP in rat milk. These results show that PTHrP is present in rat milk and also in mammary tissue before parturition, and therefore it may assist in the development of the mammary gland during pregnancy.

Production of parathyroid hormone-related protein by the rat mammary gland in pregnancy and lactation

2006 ◽  
Vol 263 (6) ◽  
pp. E1077-E1085 ◽  
Author(s):  
M. Rakopoulos ◽  
S. J. Vargas ◽  
M. T. Gillespie ◽  
P. W. Ho ◽  
H. Diefenbach-Jagger ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Parathyroid Hormone ◽  
Mammary Tissue ◽  
Secretory Cells ◽  
Related Protein ◽  
Sprague Dawley ◽  
Parathyroid Hormone Related Protein ◽  
Pregnancy And Lactation ◽  
Rat Mammary Gland ◽  
In Pregnancy

Production of parathyroid hormone-related protein by the rat mammary gland in pregnancy and lactation. Am. J. Physiol. 263 (Endocrinol. Metab. 26): E1077-E1085, 1992.--Production of parathyroid hormone-related protein (PTHrP) by the mammary gland of Sprague-Dawley rats has been examined using immunohistochemistry and in situ hybridization to detect PTHrP and PTHrP mRNA, respectively. PTHrP and PTHrP mRNA could be demonstrated in nests of epithelial cells of the developing mammary gland at day 14 of pregnancy and in the epithelial secretory cells lining the alveoli during the latter stages of pregnancy and during lactation. A specific radioimmunoassay was also used to measure the concentration of PTHrP secreted in the milk throughout lactation. The concentration of PTHrP in milk was relatively low initially but increased during the latter stages of lactation, whereas calcium concentrations remained virtually constant throughout lactation. No correlation was found between the concentrations of calcium and PTHrP in rat milk. These results show that PTHrP is present in rat milk and also in mammary tissue before parturition, and therefore it may assist in the development of the mammary gland during pregnancy.

scholarly journals Mammary gland serotonin regulates parathyroid hormone-related protein and other bone-related signals

2012 ◽  
Vol 302 (8) ◽  
pp. E1009-E1015 ◽  
Author(s):  
Laura L. Hernandez ◽  
Karen A. Gregerson ◽  
Nelson D. Horseman
Keyword(s):  
Breast Cancer ◽  
Mammary Gland ◽  
Parathyroid Hormone ◽  
Epithelial Cells ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Related Protein ◽  
Bone Demineralization ◽  
Parathyroid Hormone Related Protein ◽  
Pthrp Expression

Breast cells drive bone demineralization during lactation and metastatic cancers. A shared mechanism among these physiological and pathological states is endocrine secretion of parathyroid hormone-related protein (PTHrP), which acts through osteoblasts to stimulate osteoclastic bone demineralization. The regulation of PTHrP has not been accounted for fully by any conventional mammotropic stimuli or tumor growth factors. Serotonin (5-HT) synthesis within breast epithelial cells is induced during lactation and in advancing breast cancer. Here we report that serotonin deficiency (knockout of tryptophan hydroxylase-1) results in a reduction of mammary PTHrP expression during lactation, which is rescued by restoring 5-HT synthesis. 5-HT induced PTHrP expression in lactogen-primed mammary epithelial cells from either mouse or cow. In human breast cancer cells 5-HT induced both PTHrP and the metastasis-associated transcription factor Runx2/Cbfa1. Based on receptor expression and pharmacological evidence, the 5-HT2 receptor type was implicated as being critical for induction of PTHrP and Runx2. These results connect 5-HT synthesis to the induction of bone-regulating factors in the normal mammary gland and in breast cancer cells.

Ets-1 activates parathyroid hormone-related protein gene expression in tumorigenic breast epithelial cells

2003 ◽  
Vol 204 (1-2) ◽  
pp. 155-168 ◽  
Author(s):  
Christophe Cataisson ◽  
Johnthan Gordon ◽  
Mickael Roussière ◽  
Arman Abdalkhani ◽  
Ralph Lindemannn ◽  
...  
Keyword(s):  
Gene Expression ◽  
Parathyroid Hormone ◽  
Epithelial Cells ◽  
Protein Gene ◽  
Related Protein ◽  
Breast Epithelial Cells ◽  
Parathyroid Hormone Related Protein ◽  
Breast Epithelial

scholarly journals Parathyroid hormone-related protein regulates intestinal calcium transport in sea bream (Sparus auratus)

2006 ◽  
Vol 291 (5) ◽  
pp. R1499-R1506 ◽  
Author(s):  
Juan Fuentes ◽  
Joana Figueiredo ◽  
Deborah M. Power ◽  
Adelino V. M. Canário
Keyword(s):  
Parathyroid Hormone ◽  
Calcium Transport ◽  
Calcium Uptake ◽  
Sea Bream ◽  
Whole Body ◽  
Related Protein ◽  
Parathyroid Hormone Related Protein ◽  
Intestinal Calcium Transport ◽  
Sparus Auratus

Parathyroid hormone-related protein (PTHrP) is a factor associated with normal development and physiology of the nervous, cardiovascular, immune, reproductive, and musculoskeletal systems in higher vertebrates. It also stimulates whole body calcium uptake in sea bream ( Sparus auratus) larvae with an estimated 60% coming from intestinal uptake in seawater. The present study investigated the role of PTHrP in the intestinal calcium transport in the sea bream in vitro. Unidirectional mucosal-to-serosal and serosal-to-mucosal 45Ca fluxes were measured in vitro in duodenum, hindgut, and rectum mounted in Ussing chambers. In symmetric conditions with the same saline, bathing apical and basolateral sides of the preparation addition of piscine PTHrP 1–34 (6 nM) to the serosal surface resulted in an increase in mucosal to serosal calcium fluxes in duodenum and hindgut and a reduction in serosal to mucosal in the rectum, indicating that different mechanisms are responsive to PTHrP along the intestine. In control asymmetric conditions, with serosal normal and mucosal bathed with a saline similar in composition to the intestinal fluid, there was a net increase in calcium uptake in all regions. The addition of 6 nM PTHrP 1–34 increased net calcium uptake two- to threefold in all regions. The stimulatory effect of PTHrP on net intestinal calcium absorption is consistent with a hypercalcemic role for the hormone. The results support the view that PTHrP, alone or in conjunction with recently identified PTH-like peptides, counteracts in vivo the hypocalcemic effects of stanniocalcin.

Parathyroid hormone-related protein increases cAMP production in mammary epithelial cells

1993 ◽  
Vol 264 (3) ◽  
pp. E471-E475 ◽  
Author(s):  
S. Ferrari ◽  
R. Rizzoli ◽  
C. Chaponnier ◽  
G. Gabbiani ◽  
J. P. Bonjour
Keyword(s):  
Parathyroid Hormone ◽  
Epithelial Cells ◽  
Breast Tissue ◽  
Mammary Epithelial Cells ◽  
Mammary Epithelial ◽  
Immunofluorescent Staining ◽  
Regulatory Function ◽  
Related Protein ◽  
Camp Production ◽  
Parathyroid Hormone Related Protein

Parathyroid hormone-related protein (PTHrP) is a major cause of malignant hypercalcemia but has been found in many nontumoral tissues as well. Thus it is produced by the mammary gland during lactation and released into milk. Whether PTHrP directly affects breast tissue is however not known. We investigated the effects of PTHrP on adenosine 3',5'-cyclic monophosphate (cAMP) production in primary cultures of mammary epithelial cells isolated from lactating rats. On the 7th day in culture, synthetic PTHrP-(1-34), recombinant (r) PTHrP-(1-108), and rPTHrP-(1-141) stimulated cAMP production in a concentration-dependent manner. Thus PTHrP-(1-34) induced a 1.92 +/- 0.04-fold stimulation of cAMP production (mean +/- SE, n = 5 separate experiments, P < 0.001). At the time of maximal responsiveness to PTHrP, a significant proportion of the cells was characterized by an elongated shape and a positive immunofluorescent staining for both prekeratin and alpha-smooth muscle actin 1, compatible with a myoepithelial phenotype. It therefore appears that PTHrP can stimulate the production of cAMP in mammary cells, suggesting a possible autocrine/paracrine regulatory function for PTHrP in breast tissue.

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