HORMONES INVOLVED IN BONE

METABOLISM

by Yapa Wijeratne

Faculty of MedicineUniversity of Peradeniya Sri Lanka

1. PTH

2. Calcitriol

3. Calcitonin

4. Oestrogen

5. Cortisol ( glucocorticoids)

6. Thyroid hormones

7. Insulin

8. GH

9. IGF

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)

1-84 1-34

carboxy terminal fragment

35-84

PTH

Act directly on bones –

1. ↑osteoclast (OC) activity to ↑bone resorption → ↑mobilize [Ca+2] → ↑[Ca+2]serum

2. ↓Reabsorption of [PO4-3]in PCT

3. ↑Reabsorption of [Ca+2] in DCT

4. ↑ formation of 1,25 DHCC & this ↑ [Ca+2] absorption from the intestine.

2.Calcitriol

1. ↑Transcription of calbinding D protein in the intestine.

2. ↑Intestinal Ca+2 absorption by facilitating Ca+2

transport.

3. Facilitates Ca+2 reabsorption in the kidney.

4. ↑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].

1. Inhibit OC bone resorption

2. ↑Ca+2 Excretion in the urine

4.Estrogen

1. ↑OB functions

2. ↓OC functions

3. ↓Renal excretion of Ca+2 & PO4-3

4. ↓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.

1. ↓bone formation by inhibiting protein synthesis in OB.

2. ↓Absorption of Ca+2 & PO4-3 from the intestine

3. ↑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

1. Stimulate Growth without GH

2. Stimulate Protein synthesis in bone

3. Has stimulatory effect on1. Hematopoiesis

2. Ovarian steroidogenesis

3. Myoblast proliferation

4. 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.