PTHrP and PTH/PTHrP Receptor Expressions in Human Endometrium.

Abstract

Abstract.We investigated menstrual cycle-dependent changes in the expression of PTHrP and PTH/PTHrP receptor in the human endometrium by immunohistochemistry, and competitive reverse transcription and polymerase chain reaction (RT-PCR).Human endometrial tissues were obtained from patients who underwent gynecological surgery due to cervical cancer (carcinoma in situ) or ovarian cancer. The mean age of the 20 patients was 36.5 (range 31-44) years. For analysis of mRNA expression, specimens from proliferative (mid, n=5; late, n=5) and secretory (early, n=4; mid, n=4) phases were used. Immunohistochemical expression of PTHrP and PTH/PTHrP receptor was observed in the cytoplasm of both epithelial and stromal cells. Stronger staining of PTHrP was found in glandular epithelial cells than in stromal cells. The staining during the proliferative phase was stronger than that in the secretory phase and the difference was particularly remarkable when comparing samples from the same patient. PTH/PTHrP receptor was also present in both epithelial and stromal cells of the endometrium. However, no difference was observed in receptor expression between the proliferative and secretory phases. Competitive RT-PCR revealed that the expression of PTHrP mRNA was higher during the proliferative phase than in the secretory phase, although no difference was observed in PTH/PTHrP receptor mRNA expression. The data suggest that endometrial proliferation may be mediated by a local PTHrP autocrine and/or paracrine mechanism.

Paraneoplastic Humorally Mediated Hypercalcemia Induced by Parathyroid Hormone-Related Protein in Gynecologic Malignancies: A Systematic Review

“…Moreover, the isoforms may have diverse effects because of thevariationsintheirfunctionaldomains [6].Overproduced PTH-rPbindsthroughitsN-terminalparttothePTH/PTH-rP receptorsinboneandkidney,causinganincreaseinboneresorptionandinrenalcalciumreabsorption,leadingtohypercalcemia [6,37].PTH-rPisexpressedandsecretedbyavariety ofnormalhumantissues,includingamnion,chorion,placenta, myometrium and decidua during pregnancy. PTH-rP is also producedbynormalendometriumwithacyclicalexpression patternduringthenormalmenstrualcycle [7,8]. Tumors most commonly complicated by HHM are squamous cell carcinomas, renal cancer, endometrial cancer, humanT-lymphotropicvirus(HTLV)-associatedlymphoma, breast and ovarian cancer [3].…”

“…HHMisdefinedbyhypercalcemia,absenceofskeletalmetastases,lowPTHandelevatedPTH-rPserumlevels [7].IncreasedPTH-rPproducedathighlevelsbythemalignantcells then circulates and binds through its N-terminal part to the commonPTH/PTH-rPreceptorsinboneandkidney;thus,it mimicsPTHactionandcausesanincreaseinboneresorption and in renal calcium reabsorption, leading overall to hypercalcemia [8].Malignantgynecologicneoplasmsoftheuterus, ovary,vulvaandvaginahavebeenreportedtobecomplicated by HHM. Among them, ovarian carcinomas seem to be the mostcommontumorsassociatedwithHHM.AlthoughseveralcasereportsofgynecologicmalignancieswithsecondaryhypercalcemiaduetoparaneoplasticsecretionofPTH-rPhave beenreportedintheliterature,therearenolargepublished series,mostlybecauseoftherarityofthisclinicalentity.Inthe currentstudy,weperformedareviewoftheliteratureabout the published cases of gynecologic malignancies diagnosed withHHMandfurtherinvestigatedtheroleofhypercalcemia andPTH-rPserumlevelsonthepatients'outcome.…”

Gene expression profiling of bovine endometrium during the oestrous cycle: detection of molecular pathways involved in functional changes

“…Most of the data in the literature, although mainly derived from studies in other species, were in line with the results of the present study. Cycle-dependent expression with a higher level in proliferative in comparison with secretory phase endometrium was shown for example for CTSK (cathepsin K) (Jokimaa et al 2001), PRSS11 (serine protease 11, insulin-like growth factor (IGF) binding) (De Luca et al 2003), PTHLH (parathyroid hormone-like hormone) (Hoshi et al 2001), GJA1 (connexin 43) (Jahn et al 1995), and TNC (tenascin C) mRNAs (Taguchi et al 1999) in humans, and SPARC (osteonectin), COL5A2, COL6A3, LGALS1 (galectin 1) and SOX4 mRNAs in the Rhesus monkey (Ace & Okulicz 2004). In sheep, GRP (gastrin-releasing peptide) mRNA (Whitley et al 1998) and IGFBP6 (IGF-binding protein-6) mRNA (Gadd et al 2002) showed maximal concentrations in the endometrium around ovulation.…”

A case of groans, moans and stones with malignant undertones: Endometrioid carcinoma-associated hypercalcemia

“…The physiological and pathophysiological role of PTHrP in the female reproductive system has been investigated. PTHrP has been found to be expressed in the normal endometrium with a cyclical expression pattern during the menstrual cycle (9). This peptide has also been shown to affect myometrium contractility and to dilate placental blood vessels.…”