By COS-7 expression using an opossum kidney cell cDNA library, Juppner et al. (1991) cloned the cDNA encoding a 585-amino acid receptor for parathyroid hormone and for parathyroid hormone-related protein. The molecule has 7 potential membrane-spanning domains. The expressed receptor bound PTH and PTHLH with equal affinity, and both ligands equivalently stimulated adenylate cyclase. A striking homology with the calcitonin receptor and the secretin receptor and a lack of homology with other G protein-linked receptors indicated that these are related and represent a new family. PTHR is a member of a family of G protein-coupled receptors that includes receptors for secretin, growth hormone-releasing hormone, vasoactive intestinal polypeptide, type 1, gastric-inhibitory polypeptide, glucagon-like peptide 1, glucagon, corticotropin-releasing factor, and pituitary adenylate cyclase activating
peptide 1.
NCBI Summary:
The PTHR1 gene encodes a receptor for both parathyroid hormone (MIM 168450) and parathyroid hormone-related protein (MIM 168470).[supplied by OMIM]
General function
Receptor
Comment
Cellular localization
Plasma membrane
Comment
Ovarian function
Steroid metabolism, Oogenesis
Comment
Watson PH, et al 2001 reported the expression of PTHrP and PTHR (PTH/PTHrP-r) mRNAs and
polypeptides in bovine ovary and stimulation of bovine
blastocyst development in vitro following PTHrP treatment
during oocyte maturation.
mRNAs encoding PTHrP and PTHR
were detected by in situ hybridization methods in oocytes, and granulosa cells
in all follicles from primordial to large antral. PTHrP and PTHR polypeptides
displayed distinct distribution patterns with PTHrP polypeptides primarily
confined to oocytes from primordial to large antral follicles. PTHrP polypeptides were detectable but at a reduced level in ovarian stroma and in
granulosa and thecal layers. PTHR polypeptides were detected in oocytes of all follicular stages but were predominantly found in ovarian stroma, granulosa
and theca follicular layers. Supplementation of serum-free cSOFMaa oocyte
maturation medium with PTHrP (1-141) resulted in a concentration-dependent
increase in development to the blastocyst stage in vitro. The results suggest
that granulosa cells may be a primary site of PTHrP production and release.
Oocytes from all follicular stages stained strongly for PTHrP polypeptides and
PTHrP enhanced development to the blastocyst stage in vitro.
Expression regulated by
Comment
Endocrine meeting. [P3-252] Characterization of Parathyroid Hormone-2 Receptor in the Rodent Ovary: FSH Regulation and Effects on Granulosa Cell Function.
Mark Paciga, Ted B Usdin. Lab of Genet, NIMH NIH, Bethesda, MD
The parathyroid hormone-2 receptor (PTH2R) is a G-protein coupled receptor with a physiological role that has not been fully elucidated. Although PTH2R is expressed and synthesized at highest levels in the central nervous system, studies from our laboratory have indicated the presence of PTH2R messenger RNA in peripheral endocrine tissues. In the rodent reproductive system PTH2R gene expression was detected over the epithelium of spermatic tubules, Leydig cells and sperm cells within the lumen of the epididymus. PTH2R gene expression was also detected in the placenta and ovary. Based on these observations it is possible that PTH2R and its natural ligand, tuberoinfundibular peptide of 39 residues (TIP39), modulate some function(s) of the reproductive system via endocrine and / or autocrine / paracrine mechanisms. Therefore the objectives of this study were to determine the cellular localization of PTH2R in the rodent ovary, to determine whether ovarian PTH2R mRNA levels are affected by mediators of ovarian physiology, and to determine which aspect of ovarian function the TIP39-PTH2R ligand-receptor system modulates. Immunohistochemical analysis of rodent ovary cryosections indicated that only granulosa cells of pre-ovulatory follicles contained PTH2R-immuno positive cells. Real-time PCR analysis of primary cultures of rat granulosa cells revealed the presence of PTH2R levels under basal culture conditions. Exposure of rat granulosa cell cultures to FSH (48 hours; 100 ng/mL) resulted in a significant increase in PTH2R gene expression compared to control cultures. Similar stimulatory effects of FSH on PTH2R expression was observed in the KK-1 mouse granulosa cell line. KK-1 cells also demonstrated the presence of a functional PTH2R signal transduction pathway as indicated by an increase in cAMP levels in cells incubated with TIP39. Although TIP39 did not alter basal steroid production, FSH-stimulated estradiol accumulation in the culture media of rat primary granulosa cells was significantly reduced by TIP39 (∼7500 pg/mL in control cultures vs. ∼2500 pg/mL in TIP39 treated cultures). The results presented in this study indicate that in the rodent ovary PTH2R is localized to the granulosa cell compartment where its expression is FSH regulated. The observation that TIP39 was able to decrease FSH-stimulated estradiol output by granulosa cells suggests that the TIP39-PTH2R system may affect reproductive function via its effects on steroidogenesis.
Ovarian localization
Granulosa, Theca, Luteal cells
Comment
Garmey et al. 2000 found that PTH-rp receptor transcripts were most abundant in corpora lutea and theca cells, and least abundant (albeit detectable) in granulosa cells. Urena et al. (1993) reported that PTH/PTHrP receptor transcripts are highly expressed in PTH target tissues, kidney and bone. Receptor transcripts, however, also are expressed in many other tissues, including aorta, adrenal gland, bladder, brain, cerebellum, breast, heart, ileum, liver, lung, skeletal muscle, ovary, placenta, skin, spleen, stomach, uterus, and testes.
Follicle stages
Secondary, Antral, Preovulatory
Comment
Phenotypes
Mutations
2 mutations
Species: mouse
Mutation name: None
type: null mutation fertility: embryonic lethal Comment:Lanske et al. (1996) investigated the functions of the PTH/PTHRP receptor by deletion of the murine gene by
homologous recombination. Most PTH/PTHRP receptor -/- mutant mice died in mid-gestation, a phenotype not
observed in PTHRP -/- mice, perhaps because of the effects of maternal PTHRP. Mice that survived exhibited
accelerated differentiation of chondrocytes in bone.
Species: human
Mutation name: None
type: naturally occurring fertility: None Comment:Jobert et al. (1998) reported the absence of functional parathyroid hormone (PTH)/PTH-related peptide (PTHrP) receptors (PTH/PTHrP receptor) in Blomstrand chondrodysplasia, a genetic disorder characterized by advanced endochondral bone maturation.