In the gilthead sea bream (Sparus auratus) 17β-estradiol (E₂) plays an important role in the synthesis of vitellogenin. During vitellogenesis, vitellogenin as a nutritional precursor protein is loaded with calcium, which requires elevated plasma calcium levels. This is accomplished via E₂-dependent processes. Reports have shown that hypercalcemic effects of E₂ are possibly mediated by another hypercalcemic factor, viz. parathyroid hormone related protein (PTHrP). To further investigate the possibility of PTHrP as a mediator of E₂-induced hypercalcemia, we investigated the local expression levels of the pthrp mRNA and of the gene coding for the PTHrP receptor, PTH1R (pth1r) in two tissues involved in the calcium regulation (gills, pituitary gland) of the sea bream treated with E₂. Compared to control, treatment with E₂ resulted in: significantly increased total calcium and plasma PTHrP levels (P<0.01), a down-regulation of pthrp mRNA in the pituitary gland (P<0.01), and up-regulation of expression levels for both pthrp and pth1r in the branchial system (P<0.05). These findings provide direct evidence for a mediating role of PTHrP in E₂ induced hypercalcemia, and in addition support the idea for the presence of two independent systems, an endocrine pituitary PTHrP system and a peripheral paracrine branchial PTHrP system.

http://www.ncbi.nlm.nih.gov/pubmed/21658390?dopt=Abstract