hormones affecting blood cell production & function

Hormones Affecting Blood Cell Production &

Function

Hormones

• Erythropoietin

• Leukopoietin

• Thymosin

Erythropoietin

• 165 amino acid glycoprotein, MW = 30,000

• Produced primarily by peritubular capillary endothelial cells (Kidney)

• Minor production by Liver

• Receptor with a single transmembrane domain– Requires dimerization like PRL/GH receptor– Binds to and activates JAK-2

Erythropoietin Action

• In concert with other growth factors– Stimulates growth and maturation of

erythroblast line– Stimulates growth of megakaryocyte– Stimulates the initiation of

megakaryocyte process formation

Erythropoietin Control

PERITUBULARCAPILLARY

ENDOTHELIUM

pO2 pO2

ERYTHROBLASTLINE

ERYTHROPOIETIN

RBCs

Leukopoietin

• Postulated to Exist

• Stimulate production of Myeloid cells.

Thymic Hormones

• Thymic ablation in adult animals had no observable effect.

• Neonatal Thymectomy– Wasting Disease– Death from opportunistic infections

• Wasting Disease also after radiation & thymectomy.

• Wasting Disease prevented by thymic extracts--Thymosin

Thymosins

• Thymosin Fraction 5:– Crude preparation of 40-60 peptides– Enhances natural killer cell (NK-cell)

activity.– Stimulates secretion of Interleukin-2

(IL2) production– Stimulates IL2 receptor expression– Stimulates IL1 and tumor necrosis

factor (TNF) production

Thymosins (Cont.)

• Thymosin-alpha-1– 28 amino acid peptide– 113 amino acid prohormone,

prothymosin alpha– Induces differentiation of T-cell

precursors– Stimulates production of IL2, IL2

receptor & B-cell growth factor– Helper (CD4+) and cytotoxic (CD8+) T-

cells are target

Thymosins (Cont.)

• Thymosin-alpha-1 (Cont.)– Increases efficiency of antigen presentation

by antigen presenting cells– Paracrine/autocrine factor– Regulation not known

Thymosins (Cont.)

• Beta-thymosins– Group of related proteins who’s effect

on lymphocytes is poorly understood– May be induced by interferon– Thymosin-Beta-4 acts on differentiation

and maturation of early T-cells– Many of the beta-thymosins are

expressed by tumor cells and may be involved in metastasis.

Other Thymic Peptides

• Thymostimulin (TP-1)– Enhanced production of IL2 and interferon– Reduces postoperative infection rates of

immunocompromised patients

• Thymopoietin– Stimulates differentiation of T-cells while

inhibiting differentiation of B-cells– Increased IL2 and IL2 receptor expression– Increased size of T-cell pool– Increased NK-cell activity.

Other Thymic Peptides

• Thymulin (Serum thymic factor)– Increases T-cell populations probably

via stimulation of IL1– Production stimulated by PRL & GH

AIDS

• Thymic peptides have been used to enhance the immune system of HIV infected individuals.