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 PERITUBULAR CAPILLARY ENDOTHELIUM ERYTHROPOIETIN ERYTHROBLAST LINE 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) Thymopoietin 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.