Human PTH gene regulation in vivo using transgenic mice.

To study the regulation of the human PTH (hPTH) gene in vivo, we generated transgenic mice with the hPTH gene expressed in the mouse parathyroid using a bacterial artificial chromosome (BAC) containing the hPTH gene within its 144-kb chromosomal region. The BAC construct maintains the native hPTH gene surrounding sequences and isolates it from positional effects. The transgenic mice had normal levels of serum mouse PTH (mPTH) in addition to both intact and bioactive hPTH.

The calcium-sensing receptor regulates parathyroid hormone gene expression in transfected HEK293 cells.

Background: The parathyroid calcium receptor determines parathyroid hormone secretion and the response of parathyroid hormone gene expression to serum Ca2+ in the parathyroid gland. Serum Ca2+ regulates parathyroid hormone gene expression in vivo post-transcriptionally affecting parathyroid hormone mRNA stability through the interaction of trans-acting proteins to a defined cis element in the parathyroid hormone mRNA 3'-untranslated region. These parathyroid hormone mRNA binding proteins include AUF1 which stabilizes and KSRP which destabilizes the parathyroid hormone mRNA.

Fibroblast growth factor 23 acts on the parathyroid to decrease parathyroid hormone secretion.

Purpose Of Review: The aim of this article is to describe the intriguing action of fibroblast growth factor 23 on the parathyroid.

Recent Findings: Fibroblast growth factor 23 inhibits renal phosphate reabsorption and calcitriol production. It is the principal phosphaturic factor in a bone-kidney axis coordinating systemic phosphate homeostasis and bone mineralization.

The parathyroid is a target organ for FGF23 in rats.

Phosphate homeostasis is maintained by a counterbalance between efflux from the kidney and influx from intestine and bone. FGF23 is a bone-derived phosphaturic hormone that acts on the kidney to increase phosphate excretion and suppress biosynthesis of vitamin D. FGF23 signals with highest efficacy through several FGF receptors (FGFRs) bound by the transmembrane protein Klotho as a coreceptor.

Increased parathyroid hormone gene expression in secondary hyperparathyroidism of experimental uremia is reversed by calcimimetics: correlation with posttranslational modification of the trans acting factor AUF1.

Most patients with chronic kidney disease develop secondary hyperparathyroidism with disabling systemic complications. Calcimimetic agents are effective tools in the management of secondary hyperparathyroidism, acting through allosteric modification of the calcium-sensing receptor (CaR) on the parathyroid gland (PT) to decrease parathyroid hormone (PTH) secretion and PT cell proliferation. This study showed that rats that were fed an adenine high-phosphorus diet had increased serum PTH and PTH mRNA levels at 7 and 21 d.

Calcineurin Abeta is central to the expression of the renal type II Na/Pi co-transporter gene and to the regulation of renal phosphate transport.

The sensing and response to extracellular phosphate (Pi) concentration is preserved from prokaryotes to mammals and ensures an adequate supply of Pi in the face of large differences in its availability. In mammals, the kidneys are central to Pi homeostasis. Renal Pi reabsorption is mediated by a Na/Pi co-transporter that is regulated by a renal Pi sensing system and humoral factors.