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61

- fetal growth regulator; increased by PRL GH and somatomedins can act both in cooperation and independently to stimulate pathways that lead to growth

IGF-II

62

Stimulate GH Secretion

- decreased glucose
- decreased FFA
- increased AA
- starvation, fasting and protein deficiency
- Stress
- Excitement
- Deep Sleep (stages 3 or 4)
- Puberty
- Estrogen, androgen and thyroid hormone
- GABA
- Enkephalins
- Prostaglandin

63

Neurotransmitters that stimulate GH secretion

Dopamine
Acetylcholine
Serotonin
Norepinephrine

64

Inhibit GH secretion

- Somatostatin
- Increased glucose and FFA
- Somatomedins (IGF)
- GH
- Beta adrenergic agonist
- Cortisol
- Senescence
- Obesity
- Pregnancy

65

- Excessive activation of somatotropes or (+) acidophilic pituitary tumors
- Excessive GH before puberty/ fusion of epiphyses with shaft
- Rapid growth of all body tissues
- Hyperglycemia due to Eventual degeneration of overactive pancreas and can lead to DM
- Panhypopituitarism in most, if untreated: Death by early adulthood

Gigantism

66

other cells in the pituitary are unfunctional

Panhypopituitarism

67

Management for Gigantism

- microsurgical tumor removal
- Pituitary gland irradiation

68

- Excessive GH after puberty / epiphyseal fusion with shaft

- Thicker and enlarged bones
Hands, feet
Membranous bones (cranium, nose, forehead, supraorbital ridge, mandible, vertebrae)

- Continued growth of soft tissues (tongue, liver, kidneys)
- Prognathism, huge brows, huge tongue, large hands with spade fingers
- Deep guttural voice
- Oily skin

Acromegaly

69

- a type of GH excess
- Joint deformities or frank arthritis
- Secondary DM
- Sleep apnea
- Kyphosis

↑ coronary risk:
- Poor glucose tolerance
- Hypertension
- Lipid problems

- Life shorter by average 10 years (vs. normal person)

Acromegaly

70

Management for Acromegaly

Normalized by treatment of adenoma (surgery, octreotide, radiation)

Ocreotide - somatotropin analog

71

If adult onset – typically with other Anterior Pituitary hormone deficiencies

If childhood onset – dwarfism

Growth Hormone Deficiency

72

- ↓ secretion of all AP hormones
- May be congenital, slowly or suddenly develop

Panhypopituitarism

73

Causes of Panhypotituitarism

- Pituitary tumor
- Suprasellar cysts
- Enlarged Rathke’s pouch remnants
- Pituitary infarction and necrosis from post-partum hemorrhage (Sheehan syndrome)

74

Causes:

Panhypopituitarism during childhood
- Hypothalamic dysfunction, GHRH deficiency
- Pituitary destruction, GH deficiency

Isolated GH deficiency
- Biologically incompetent GH
- GH receptor deficiency

(Pituitary) Dwarfism

75

Causes
- Unresponsive GH receptor (Laron dwarf/ GH insensitivity)
- Hereditary inability to form somatomedin C (IGF-I) (African pygmy; Levi-Lorain dwarf)

(Pituitary) Dwarfism

76

(Pituitary) Dwarfism: Manifestations:

- Proportional body parts
- Short stature
- Delayed skeletal maturation
- Greatly ↓ development rate
- Does not go through puberty
- Insufficient gonadotropic hormones for sexual maturation
- If only GH deficient (1/3) → mature sexually & reproduce

77

Panhypopituitarism in Adult: Causes

- Pituitary destruction
- Tumors: Pituitary adenoma, craniopharyngioma, chromophobe tumors
- Surgery, radiation, trauma
- Sheehan’s syndrome
- Empty sella syndrome
- Stroke
- Infectious meningitis (e.g., TB meningitis)
- Vascular problems (e.g., cavernous sinus thrombosis, sarcoidosis)
- Post-surgical cure of acromegaly

78

Panhypopituitarism in Adult: Manifestation

- Hypothyroidism (e.g., lethargy)
- Depressed glucocorticoid production by adrenals (e.g., weight gain)
- Suppressed gonadotropic hormone secretion (e.g., lost sexual function)

79

Panhypopituitarism in Adult: Treatment

Most signs & symptoms treatable by adrenocortical and thyroid hormones

80

Medical Uses of Human Growth Hormone

1. Dwarfism and replacement therapy in growth-deficient children - Human GH synthesized by E. coli
- if purely GH deficiency → completely treatable if given early

2. Turner's syndrome -2nd X chromosome in females either absent or deformed → growth & development problems

3.Renal insufficiency (kidney failure)

4. HIV - to treat muscle wasting

81

Medical Uses of Human Growth Hormone 2

5. Anti-aging:
- Increased protein deposition, esp. in muscles
- ↓ fat deposits
- Feeling of invigoration of energy
- GH + exercise: ↑ type II muscle fibers in elderly

6. Physical performance enhancer in sports
- Used for perceived anabolic effects on muscle growth and recovery (e.g., in weight lifting, body building, football, etc.)
- Combined with anabolic steroids, erythropoietin
- Studies: no ↑ muscle size or strength after hGH injection

82

-10-20%
Hormone product: Adrenocorticotropic Hormone (ACTH)
Stain Affinity: Basophilic
Hypothalamic Hormone Control: CRH
Target: Adrenal, Adipose
Peripheral Hormone Involved: Cortisol

Corticotrope

83

- 30-50%
Hormone product: Growth Hormone (GH) to Somatotropin
Stain Affinity: Acidophilic
Hypothalamic Hormone Control: GHRH, GHIH (somatostatin)
Target: All Tissues (major in LIVER)
Peripheral Hormone Involved: Insuline-like growth factor-I (IGF-I)

Somatotrope

84

- 10-15%
Hormone product: Follicle Stimulating Hormone (FSH); Luteinizing Hormone (LH)
Stain Affinity: Basophilic
Hypothalamic Hormone Control: GnRH
Target: GONADS

Peripheral Hormone Involved:
Estrogen
Progesterone
Testosterone
Inhibit

Gonadotrope

85

10-30%
Hormone product: Prolactin (PRL)
Stain Affinity: Acidophilic
Hypothalamic Hormone Control: PIH
Target: Breast, Gonads
Peripheral Hormone Involved: None

Lactotrope (Mammotrope)

86

3-5%
Hormone product: Thyroid Stimulating Hormone (TSH)
Stain Affinity: Basophilic
Hypothalamic Hormone Control: TRH
Target: Thyroid Gland
Peripheral Hormone Involved: Triode-thyronine

Thyrotrope

87

▪ Also called the Neurohypophysis
▪ Composed mainly of glial-like cells called pituicytes

POSTERIOR PITUITARY GLAND

88

▪ do not secrete hormones
▪ act to support large numbers of terminal nerve fibers and terminal nerve endings from nerve tracts that originate in the supraoptic and paraventricular nuclei of the hypothalamus

Pituicytes

89

▪ Anti-diuretic hormone (ADH) or vasopressin and Oxytocin
▪ Synthesized in the cell bodies of the supraoptic and paraventricular nuclei
▪ Transported with “carrier” proteins called NEUROPHYSINS down to the nerve endings in the neurohypophysis (requires several days)

Neurohypophysial Hormones

90

▪ ADH is formed primarily in the supraoptic nuclei
▪ Oxytocin is formed primarily in the paraventricular nuclei
▪Each of these nuclei can synthesize about one sixth as much of the second hormone as of its primary hormone

Neurohypophysial Hormones