Transcript 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
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.