1. Hormones Affecting Blood Cell Production & Function

2. Hormones
Erythropoietin
Leukopoietin
Thymosin

3. 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

4. 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

5. Erythropoietin Control
PERITUBULAR
CAPILLARY
ENDOTHELIUM
ERYTHROPOIETIN
ERYTHROBLAST
LINE
RBCs

6. Leukopoietin Postulated to Exist
Stimulate production of Myeloid cells.

7. 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

8. 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

9. 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

10. Thymosins (Cont.) Thymosin-alpha-1 (Cont.)
Increases efficiency of antigen presentation by antigen presenting cells
Paracrine/autocrine factor
Regulation not known

11. 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.

12. 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.

13. Other Thymic Peptides Thymulin (Serum thymic factor)
Increases T-cell populations probably via stimulation of IL1
Production stimulated by PRL & GH

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