Hormones Affecting Blood Cell Production & Function

Hormones

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Erythropoietin Leukopoietin Thymosin

Erythropoietin

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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

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Requires dimerization like PRL/GH receptor

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Binds to and activates JAK-2

Erythropoietin Action

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In concert with other growth factors

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Stimulates growth and maturation of erythroblast line

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Stimulates growth of megakaryocyte

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Stimulates the initiation of megakaryocyte process formation

Erythropoietin Control

pO 2 pO 2 PERITUBULAR CAPILLARY ENDOTHELIUM ERYTHROPOIETIN ERYTHROBLAST LINE RBCs

Leukopoietin

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Postulated to Exist Stimulate production of Myeloid cells.

Thymic Hormones

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Thymic ablation in adult animals had no observable effect.

Neonatal Thymectomy

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Wasting Disease

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Death from opportunistic infections Wasting Disease also after radiation & thymectomy.

Wasting Disease prevented by thymic extracts--Thymosin

Thymosins

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Thymosin Fraction 5:

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Crude preparation of 40-60 peptides

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Enhances natural killer cell (NK-cell) activity.

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Stimulates secretion of Interleukin-2 (IL2) production

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Stimulates IL2 receptor expression

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Stimulates IL1 and tumor necrosis factor (TNF) production

Thymosins (Cont.)

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Thymosin-alpha-1

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28 amino acid peptide

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113 amino acid prohormone, prothymosin alpha

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Induces differentiation of T-cell precursors

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Stimulates production of IL2, IL2 receptor & B-cell growth factor

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Helper (CD4+) and cytotoxic (CD8+) T cells are target

Thymosins (Cont.)

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Thymosin-alpha-1 (Cont.)

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Increases efficiency of antigen presentation by antigen presenting cells

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Paracrine/autocrine factor

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Regulation not known

Thymosins (Cont.)

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Beta-thymosins

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Group of related proteins who’s effect on lymphocytes is poorly understood

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May be induced by interferon

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Thymosin-Beta-4 acts on differentiation and maturation of early T-cells

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Many of the beta-thymosins are expressed by tumor cells and may be involved in metastasis.

Other Thymic Peptides

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Thymostimulin (TP-1)

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Enhanced production of IL2 and interferon

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Reduces postoperative infection rates of immunocompromised patients Thymopoietin

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Stimulates differentiation of T-cells while inhibiting differentiation of B-cells

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Increased IL2 and IL2 receptor expression

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Increased size of T-cell pool

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Increased NK-cell activity.

Other Thymic Peptides

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Thymulin (Serum thymic factor)

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Increases T-cell populations probably via stimulation of IL1

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Production stimulated by PRL & GH

AIDS

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