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31

(Regulation of Hormone Receptors)

Decrease in:
- Receptor Number
- Receptor Affinity
- E.g. in the uterus, progesterone down-regulates its own receptor and the receptor for estrogen

DOWN-REGULATION OF RECEPTORS

32

(Regulation of Hormone Receptors)

Increase in:
- Receptor Number
- Receptor Affinity
- E.g. in the ovary, estrogen up-regulates its own receptor and that of LH

UP-REGULATION OF RECEPTORS

33

Hormone Interaction

1. SYNERGISTIC EFFECTS
2. PERMISSIVE EFFECTS
3. ANTAGONISTIC EFFECTS

34

SYNERGISTIC EFFECTS

ADDITIVE EFFECTS - same function
- E.g. Epinephrine and NE effects on the heart

COMPLEMENTARY EFFECTS - different function but end product is the same
- E.g. FSH and Testosterone effects on spermatogenesis

35

- permit the other hormone to do its function
- E.g. Cortisol has permissive effects on Epi and NE with regards to blood vessels; T3 has __ on Epi with regards to lipolysis

PERMISSIVE EFFECTS

36

- inhibit one another
- E.g. Estrogen blocking Prolactin effects on the breasts during pregnancy

ANTAGONISTIC EFFECTS

37

- Equal to the rate of disappearance of hormone from the plasma/concentration of hormone in each milliliter of plasma
- Mechanisms: Tissue Destruction, Tissue binding, Bile Excretion, Urine Excretion

Metabolic Clearance Rate

38

- problem pertaining to the target organ or peripheral gland

Primary Endocrine disease

39

- problem is in the pituitary gland

Secondary Endocrine Disease

40

- problem is in the hypothalamus

Tertiary Endocrine Disease

41

- Causes growth of all or most body tissues
- Prerequisite: SUFFICIENT INSULIN ACTIVITY and CHO
- Stimulates increased: MITOSIS, CELL SIZE AND CELL NUMBER
- Promotes differentiation of specific cell types (e.g., bone growth cells)
- Single chain; 191 AA residues
- Pulsatile secretion

Growth Hormone (Somatotropin)

42

- Relatively low during the day
- ↑s during first 2 hours of deep sleep
- Regular nocturnal peak: 1 hour after Stage 3 or 4 deep sleep onset
- Preceded by nocturnal plasma GHRH peak

Growth Hormone (Somatotropin)

43

- Biological t½ = 20 mins
- Serum GH level varies widely
- GH secretion in women > men
(highest before ovulation)
- Rate: highest in late puberty, neonate; lowest in older/obese adults, hypothyroidism, Type 2 DM

Growth Hormone (Somatotropin)

44

Growth Hormone (Somatotropin): AVERAGE PLASMA CONCENTRATION

- 5-20 years old: 6 ng/ml
- 20-40 years old: 3 ng/ml
- 40-70 years old: 1.6 ng/mL

45

Pattern of GH Secretion: Pre-puberty

- Stabilization of 24-hour pulsatile GH secretion rates (200-600 μg/day)
- Approximate those in post-pubertal young adults

46

Pattern of GH Secretion: Puberty

- 1.5-3-fold ↑ pulsatile GH secretion
- With proportionate ↑ in plasma insulin-like growth factor-I (IGF-I)
- Physiological GH hypersecretion driven by onset of ↑ sex-steroid hormones
- Correlate with rate of ↑ in height
- GHRH response: tall adults > ave height

47

Pattern of GH Secretion: Puberty

- Final height (FH) may partly be determined by inherent GH secretory capacity
- In normal children with idiopathic short stature - GH treatment significantly ↑ FH in a dose-dependent manner

Mean gain = 1.3 SDS (8 cm) and a broad range of response from no gain to 3 SDS compared to a mean gain of 0.2 SDS in the untreated controls. (Albertsson-Wikland, 2008)

48

Pattern of GH Secretion: Adulthood

- Starting 18-25 y/o GH secretion ↓s up to pre-pubertal level (

49

Pattern of GH Secretion: Aging

- ↓ GH secretion

- Correlated to
- ↑ total body & visceral fat %; Muscle wasting, ↓ physical fitness, ↓ [testosterone ] or menopause

- Partly responsible for: ↓ lean body mass; ↓ protein synthesis; ↓ metabolic rate and ↑ adipose tissue

50

Excessive somatostatin release can lead to

↓/deficiency GHRH secretion in aging human

51

- is a Protein anabolic hormone, Lipolytic hormone, Diabetogenic hormone, Growth promoter hormone

Growth hormone

52

True or False

Linear bone growth does not happen when the epiphyseal plates close

True

53

Growth Hormone: Effect on Protein Metabolism

Anabolic
- Stimulates AA uptake and CHON deposition
- ↓ protein breakdown
- Effect begins in minutes
- Stimulates collagen synthesis

Produces:
- (+) Nitrogen balance
- ↓ BUN and AA (Amino Acids)
- ↑ excretion of AA 4-hydroxyproline

54

Growth Hormone: Effect of Carbohydrate Metabolism

- Normal GH level needed to maintain normal pancreatic Islet function which can lead to decreased insulin if no GH
- decreased CHO use can DIABETOGENIC
- Mechanism: Impaired insulin function from increased FA blood concentration

55

Growth Hormone: Effect on Electrolyte Metabolism

- ↑ GI absorption of Ca2+
- ↓ Na+ and K+ excretion – most probably due to diversion from kidneys to growing tissues
- (+) Phosphorus balance; ↑ plasma Phosphorus

56

Growth Hormone: Effect on Fat Metabolism

- Lipolytic
- ↑ FA mobilization & use for energy
- ↑ FA to Acetyl CoA conversion
- ↑ FFA may contribute to GH-induced insulin resistance
- Effect begins in hours

57

Summary of GH Actions

1. ↑ protein synthesis rate in most body cells
2. ↓ Adiposity:
3. ↑ lipolysis / FA mobilization from adipose tissue
4. ↑ FA in blood
5. ↑ FA use as fuel
6. ↓ glucose uptake
7. ↑ linear growth
8. ↑ organ size & function
9. ↑lean body mass

58

- Mediate action of GH on chondrocytes & linear growth, protein metabolism and organ size, and lean body mass
- Polypeptide growth factors
- Secreted by liver and other tissues

Somatomedins (Insulin-like Growth Factors I & II)

59

Types of Somatomedins

1. IGF-I (Somatomedin C)
2. IGF-II

60

- skeletal and cartilage growth
- Increases in parallel with GH
- Both GH- and insulin-dependent
- Lower in old age: angina pectoris, myocardial infarction, atherosclerosis
- Earlier death in aging men with low levels

IGF-I (Somatomedin C)