1.PTH Secreted by Chief cells of the parathyroid gland 84 amino acid(AA) ↓ [Ca+2]ECF (+) secretion ↑ [PO4-3]serum PTH active PTH(amino terminal fragment) 1-841-34 carboxy terminal fragment 35-84
PTH Act directly on bones – ↑osteoclast (OC) activity to ↑bone resorption -> ↑mobilize [Ca+2] -> ↑[Ca+2]serum ↓Reabsorption of [PO4-3]in PCT ↑Reabsorption of [Ca+2] in DCT ↑ formation of 1,25 DHCC & this ↑ [Ca+2] absorption from the intestine.
2.Calcitriol ↑Transcription of calbinding D protein in the intestine. ↑Intestinal Ca+2 absorption by facilitating Ca+2 transport. Facilitates Ca+2 reabsorption in the kidney. ↑The synthetic activity of osteoblast (OB) & is necessary for normal calcification of matrix
3.Calcitonin By Parafollicular cells of thyroid gland. 32 AA Secretion is regulated by serum[Ca+2]. Inhibit OC bone resorption ↑Ca+2 Excretion in the urine
4.Estrogen ↑OB functions ↓OC functions ↓Renal excretion of Ca+2 & PO4-3 ↓intestinal excretion of Ca+2 & PTH function
5. Cortisol ( glucocorticoids) lower plasma Ca2+ levels by inhibiting osteoclast formation and activity. Over long periods they cause osteoporosis by ↓bone formation & ↑bone resorption. ↓bone formation by inhibiting protein synthesis in OB. ↓Absorption of Ca+2 & PO4-3 from the intestine ↑Renal excretion of Ca+2 & PO4-3
6. Thyroid hormones Promote normal growth and skeletal development. May cause hypercalcemia, hypercalciuria, and, in some instances, osteoporosis.
7. Insulin ↑Bone formation (via OB activity) DM -> ↓insulin -> Significant bone loss in untreated DM.
8.GH Anabolic effect on bone Promotes the growth of the skeleton These effects in are believed to be mediated by IGF I & II acting on cells of the OB. ↑urinary excretion of Ca+2 & hydroxyproline ↑Intestinal absorption of Ca+2 NET EFFECT (+) Ca+2 balance ↓urinary excretion of PO4-3
9.IGF -I Long arm of chromosome 12 & produces a 70 AA polypeptide. Receptor (®) IGF-I = insulin ® -> stimulates Tyr kinase activity & autophosporylation of the Tyr residue in ® -> cell differentiation & division
IGF-I Stimulate Growth without GH Stimulate Protein synthesis in bone Has stimulatory effect on Hematopoiesis Ovarian steroidogenesis Myoblast proliferation Differentiation of lens
IGF-II 67 AA peptide Short arm of chromosome 11 [IGF II]plasma vary with Age Physiological condition (peak during puberty) Neonates children puberty adult
IGF-BPS IGF molecules in the circulation are mostly bound to variety. IGF-BPS I (-) action of IGF I It is present in ↑ [ ] in fetal serum & amniotic fluid.