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 pO2 pO2 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+) Tcells 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.