Expression cloning of a common receptor for parathyroid hormone and parathyroid hormone-related peptide from rat osteoblast-like cells: a single receptor stimulates intracellular accumulation of both cAMP and inositol trisphosphates and increases intracellular free calcium.

Abstract

Parathyroid hormone (PTH), a major regulator of mineral ion metabolism, and PTH-related peptide (PIHrP)

PTHrP Produced by Myeloma Plasma Cells Regulates Their Survival and Pro-Osteoclast Activity For Bone Disease Progression

“…(50) It has also been reported that PTHrP activates PTH-R1 in relation to the homology of its NH 2 -terminal domain with PTH and that receptor stimulation by the PTHrP subunit (aa 1-40) results in both intracellular PKA and PKC activation. (2) We confirmed the PTH-R1 sensitivity to PTHrP in MM cells and demonstrated that the receptor is specifically susceptible to the NH 2 -terminal fragment (aa 1-40) because, in all instances, we recorded an increased influx of Ca 2þ and cAMP content. This bioactivity was not observed using the mid-region fragments, even those including NLS, nor using osteostatin, whose receptor has not yet been identified.…”

“…(1) These peptides show high homology within their NH 2 -domain in the 1-34 amino acid (aa) sequence, by which they bind the same G-protein receptor (PTH-R1). (2,3) During fetal development PTHrP is produced by perichondral cells to adjust placental calcium levels and support the differentiation of endochondral cells to chondrocytes, (4,5) whereas after birth it concurs to development of mammary glands and lactation. (6) The predominant activity of PTHrP in bone metabolism has been definitely proved in homozygous PTHrP-deficient mice that show abnormal bone morphogenesis, leading to osteopetrosis and short-term survival after birth.…”

“…Similar to PTH, the NH 2 -terminal subunit (aa avidly links PTH-R1, by which it regulates calcium channels promoting the influx of extracellular Ca 2þ , and activates both adenylate-cyclase protein A kinase (PKA) and phospholipase Cb protein kinase (PKC) pathway signals. (2) The mid-region (aa 38-106) has been reported to contain the nuclear localization sequence (aa 87-94) (NLS) that binds DNA in nuclei with potential effects on cell proliferation, because NLS À/À mice show accelerated apoptosis in most tissues, which is associated with delayed growth, senescence, and early death. (19)(20)(21) Last, the COOH-terminal subunit (aa 107-139), also known as osteostatin, has been described as a negative regulator of signals induced by the NH 2 -terminal region and an inhibitor of the osteoclast activity in rats.…”

Icariin from Epimedium brevicornum Maxim promotes the biosynthesis of estrogen by aromatase (CYP19)

“…A variety of cytokines, such as 1,25-dihydroxyvitamin D3, dexamethasone, interleukin 1b, and transforming growth factor b1 have been found to upregulate aromatase expression at the transcriptional level (Ribot et al, 2006). Parathyroid hormone, clinically used to increase bone formation and bone mass in the treatment of osteoporosis, promotes osteoblast proliferation and differentiation by stimulating intracellular cAMP production (Abou-Samra et al, 1992). cGMP and its activated PKG have also been found to regulate osteoblast proliferation and differentiation (Rangaswami et al, 2010).…”

PTHrP and the PTH/PTHrP receptor are co-expressed in human breast and colon tumours

“…PTH and PTHrP bind to the same cell-surface receptor (the type 1 PTH/PTHrP receptor) (Abou-Samra et al, 1992), and PTHrP exerts many effects on target cells in common with PTH, including elevation of intracellular cAMP (Birch et al, 1995) and [Ca2+], (Donahue et al, 1988;Schofl et al, 1991). PTHrP has been localized to a range of normal and fetal tissues (Moniz et al, 1990), but its physiological role is not yet clear.…”