Presentation is loading. Please wait.

Presentation is loading. Please wait.

MOLECULAR ENDOCRINOLOGY AND IMMUNOLOGY LECTURE 7 - Mechanism of action of growth hormone and prolactin Growth hormone: general actions; receptor; signal.

Similar presentations


Presentation on theme: "MOLECULAR ENDOCRINOLOGY AND IMMUNOLOGY LECTURE 7 - Mechanism of action of growth hormone and prolactin Growth hormone: general actions; receptor; signal."— Presentation transcript:

1 MOLECULAR ENDOCRINOLOGY AND IMMUNOLOGY LECTURE 7 - Mechanism of action of growth hormone and prolactin Growth hormone: general actions; receptor; signal transduction; IGFs Prolactin: actions on mammary gland; other actions; receptor; signal transduction Mechanism of action of cytokines

2 The GH-IGF-Somatic axis

3 GH RECEPTOR First cloned (as cDNA) from rabbit and then human liver (Leung et al 1987) signal extracellular transmembrane intracellular Shown to be the real receptor by specificity, and absence in patients with Laron dwarfism

4 Cytokine receptors

5 OVINE GH-RECEPTOR HOMOLOGY MODEL

6

7 GH-RECEPTOR INTERACTION

8 JAK Kinases Soluble tyrosine protein kinases, first named just another kinase. Subsequently janus kinases (because two apparent binding sites for ATP) JAK1 JAK2 JAK3 Tyk

9 GH Receptor and jak2 From: Herrington & Carter-Su (2001)

10 GH signalling From: Herrington & Carter-Su (2001)

11 STAT = signal transduction and activation of transcription STAT1-STAT5 In 3T3-F442A cells use of antisense knock-out of JAK2 or STAT5 eliminates GH actions. Depletion of MAPK pathway and p70 s6 kinase pathway does not

12 Regulation of GH receptor–JAK2 signaling From: Herrington & Carter-Su (2001)

13 The GH-IGF-Somatic axis

14 THE SULPHATION FACTOR/SOMATOMEDIN/IGF HYPOTHESIS Inject hypophysectomized rat with GH: induces growth and metabolism of cartilage (including incorporation of 35 SO 4 into cartilage) Incubate cartilage from hypox rat with serum from hypox rat + GH - no stimulation of cartilage metabolism Incubate cartilage from hypox rat with serum from GH-treated rat - stimulation of cartilage metabolism SO GH treatment leads to production of a factor in serum which can stimulate cartilage metabolism and growth

15 Insulin-like growth factor I and II IGF I IGF II Somatomedins Non-suppressible-insulin-like-activity (NSILA) Multiplication stimulating activity (MSA)

16 Sequence of IGF II

17 Sequences of insulin and IGFs compared

18 Precursors of insulin and IGFs proinsulin proIGF I proIGF II

19 IGF IIInsulin 3D structures of insulin and IGF

20 The GH-IGF-Somatic axis

21 Isaksson

22 The GH-IGF-Somatic axis

23 Endocrine control of mammary gland

24 Mammary gland development

25 Prolactin induces synthesis of the following proteins: Casein Alpha-lactalbumin Lactose synthase Fatty acid synthetase

26 Cytokine signalling From: Shillingford et al (2001)


Download ppt "MOLECULAR ENDOCRINOLOGY AND IMMUNOLOGY LECTURE 7 - Mechanism of action of growth hormone and prolactin Growth hormone: general actions; receptor; signal."

Similar presentations


Ads by Google