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 ◽  
...  

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.

2006 ◽  
Vol 263 (6) ◽  
pp. E1077-E1085 ◽  
Author(s):  
M. Rakopoulos ◽  
S. J. Vargas ◽  
M. T. Gillespie ◽  
P. W. Ho ◽  
H. Diefenbach-Jagger ◽  
...  

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.


1997 ◽  
Vol 64 (4) ◽  
pp. 633-636
Author(s):  
GORDON E. THOMPSON ◽  
S. KHAWAR ABBAS ◽  
CARL HOLT ◽  
ANTHONY D. CARE

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.


2001 ◽  
Vol 171 (3) ◽  
pp. 403-416 ◽  
Author(s):  
ME Dunbar ◽  
P Dann ◽  
CW Brown ◽  
J Van Houton ◽  
B Dreyer ◽  
...  

We have previously demonstrated that overexpression of parathyroid hormone-related protein (PTHrP) in the mammary glands of transgenic mice results in defects in ductal elongation and branching during puberty and in lobuloalveolar development during pregnancy. In addition, we have shown that PTHrP is necessary for the formation of the initial ductal tree during embryonic mammary development. In order to examine the effect of varying the timing of PTHrP overexpression on mammary development, we created tetracycline-regulated, K14-tTA/Tet(O)-PTHrP double transgenic mice. In this report, we document that this 'tet-off' system directs transgene expression to the mammary gland and that it is fully repressed in the presence of tetracycline. Using these mice, we demonstrate that transient overexpression of PTHrP before birth causes defects in ductal branching during puberty and that overexpression of PTHrP during puberty decreases the rate of ductal elongation. Furthermore, we demonstrate that if PTHrP overexpression is initiated after ductal morphogenesis is completed, lobuloalveolar development is unaffected. Finally, we demonstrate that the impairment in ductal elongation caused by PTHrP is associated with an increase in the basal rate of epithelial cell apoptosis in terminal end buds and a failure to increase end bud cell proliferation and decrease apoptosis in response to estrogen and progesterone.


1998 ◽  
Vol 20 (2) ◽  
pp. 271-280 ◽  
Author(s):  
SF Wojcik ◽  
FL Schanbacher ◽  
LK McCauley ◽  
H Zhou ◽  
V Kartsogiannis ◽  
...  

Parathyroid hormone-related protein (PTHrP) produced by the mammary gland has been postulated to have multiple functions in both the mother and neonate. In humans, alternative 3'-mRNA splicing and endoproteolytic processing result in multiple bioactive PTHrP peptides. Multiple PTHrP peptides also have been reported in bovine milk. To investigate the source of molecular heterogeneity of PTHrP in bovine milk, bovine PTHrP was cloned from a bovine brain cDNA library, sequenced and used to characterize the mammary PTHrP transcript. A 1065 bp clone (bP1) for bovine PTHrP was isolated from a brain cDNA library. The bP1 clone contained the entire coding sequence of PTHrP and 61 and 473 nucleotides of the 5'- and 3'-untranslated regions (UTRs) respectively. The predicted amino acid sequence of bovine PTHrP was 72-92% homologous to the sequences of chicken, rat, mouse, human, and canine PTHrP with the highest sequence divergence present in the C-terminal region of the peptide. The 5'- and 3'-UTRs of bovine brain PTHrP have a high degree of homology to exons 4 and 9 of human PTHrP respectively. PTHrP was expressed as a single 1200 nucleotide mRNA transcript in lactating bovine mammary tissue. RT-PCR using region-specific oligonucleotide primers derived from bP1 demonstrated that PTHrP mRNA transcripts in bovine brain and lactating mammary gland utilize the same 5'- and 3'-UTRs. Expression of PTHrP mRNA was localized to secretory and ductular epithelial cells within the lactating mammary gland, as detected using in situ hybridization. Expression of PTHrP mRNA was demonstrated in the mammary gland during late pregnancy and throughout lactation in cows.


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