ME04 - Anterior Pituitary Flashcards
If the infundibulum is transsected what happens?
If transsected, there will be temporary cessation»_space; neurons then regenerate but with malfunctions (more or less)
Feedback Control of AP Hormone Secretion
Stimuli»_space; Hypothalamus»_space; Anterior Pituitary»_space; Target Organ»_space; Tissues
Causes growth of all or most body tissues
Promotes differentiation of specific cell types (e.g., bone growth cells)
Single chain; 191 AA residues _
Growth Hormone (Somatotropin)
Prequisite of Growth Hormone
Sufficient insulin activity & CHO
Growth Hormone is stimulated by:
Mitosis
Cell size
Cell number
Type of secretion of GH
Pulsatile secretion
Why is GH 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
GROWTH HORMONE INFO:
Preceded by nocturnal plasma GHRH peak
Biologicalt1_2=20mins
- 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
- Average plasma concentration - 5-20 years old: 6 ng/ml
- 20-40 years old: 3 ng/ml
Lifetime Pattern of GH Secretion
40-70 years old: 1.6 ng/mL
Stabilization of 24-hour pulsatile GH secretion rates (200-600 _g/day)
Approximate those in post-pubertal young adults
Pre-puberty GH secretion
Growth Hormone in Puberty
1.5-3-fold_pulsatileGHsecretion
- With proportionate _ in plasma insulin-like growth fac- tor-I (IGF-I)
- Physiological GH hypersecretion driven by onset of _ sex-steroid hormones
- Correlatewithrateof_inheight
- GHRH response: tall adults > ave height
- 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 man- ner
- Mean gain = 1.3 SDS (8 cm) and a broad range of re- sponse from no gain to 3 SDS compared to a mean gain of 0.2 SDS in the untreated controls. (Al- bertsson-Wikland, 2008)+A12
Growth Hormone in adulthood
Starting 18-25 y/o GH secretion _s up to pre-pubertal level (
Growth Hormone in Aging
_ GH secretion - Correlated to
- _ total body & visceral fat %
- Muscle wasting
- _ physical fitness
- _ [testosterone] or menopause
- Partly responsible for: - _leanbodymass
- _ protein synthesis
- _metabolicrate
- _adiposetissue
- Evidence: (Giustina & Veldhuis, 2008)
- Excessive somatostatin release
- _/deficiency GHRH secretion in aging human
Other names for Growth Hormone
Protein anabolic hormone
Lipolytic hormone
Diabetogenic hormone
Growth promoter hormone _
Relate GH to Linear Bone Growth
GH»_space; INC chondrocytic & osteogenic cell reproduction; INC protein deposition; Chondrocyte - osteogenic cells»_space; Chondrogenesis/Osteogenesis»_space; Linear Bone Growth
Linear Bone Growth does not happen when the epiphyseal plates close. True or False?
TRUE
GH»_space; Unfused Epiphyses results to:
Gigantism
GH»_space; Fused Epiphyses results to:
Acromegaly
Effect of Growth Hormone on Protein Metabolism (ANABOLIC)
Stimulates AA uptake & CHON deposition
- _proteinbreakdown
- Effect begins in minutes
- Stimulates collagen synthesis+A19
Protein metabolism produces what products
(+) Nitrogen balance _BUN&AA _excretionofAA4-hydroxyproline
Effect of Growth Hormone on Electrolyte Metabolism
_ GI absorption of Ca2+
_ Na+ and K+ excretion most probably due to diversion from kidneys to growing tissues (+) P balance; _ plasma P
Effect of Growth Hormone on Carbohydrate Metabolism
Normal GH level needed to maintain normal pancreatic islet function»_space; decreased insulin if no GH | DEC CHO use»_space; Diabetogenic
GH-induced insulin resistance/hyperglycemia results to:
DEC Glucose uptake by tissues| INC insulin secretion | INC hepatic gluconeogenesis
Effect of Growth Hormone on Fat Metabolism
Lipolytic
_ FA mobilization & use for energy
_ FA to Acetyl CoA conversion
_ FFA may contribute to GH-induced insulin resistance
EXCESSIVE GH»_space; Large quantities of fat metabolized»_space; Liver»_space; Ketosis/Fatty Liver
GH promotes diabetogenic state. True or False
TRUE
Summary of GH Actions
_ protein synthesis rate in most body cells
_ Adiposity:
_ lipolysis / FA mobilization from adipose tissue _ FA in blood
_FA use as fuel
_ glucose uptake
_ linear growth
_ organ size & function
_lean body mass
Relate how GH»_space; Adipose Tissue»_space; DEC Adiposity
GH -> Adipose Tissue»_space; _ glucose uptake (hyperglycemic hormone)
_ lipolysis»_space; _ adiposity
Relate how GH»_space; Liver»_space; Facilitation of GH effect on:
organs (size & function) muscle (body mass) chondrocytes (linear growth)
GH -> Liver»_space; _ RNA synthesis
_ protein synthesis _ gluconeogenesis _ IGF/somatomedin»_space; Facilitation of GH effect on: organs (size & function) muscle (body mass) chondrocytes (linear growth)
Relate how GH»_space; Muscle»_space; INC lean body mass
GH -> Muscle»_space; _ glucose uptake _ AA uptake
_ protein synthesis»_space; _ lean body mass
Relate how GH»_space; Bone, heart, lung, kidney,pancreas, intestines, glands, skin, connective tissue»_space; INC Organ Size & Function
GH -> Bone, heart, lung, kidney, pancreas, intestines, glands,
skin, connective tissue»_space; _ protein synthesis _ RNA & DNA synthe- sis _ cell size and number»_space; _ organ size & function
Relate how GH»_space; Chondrocytes»_space; INC Linear Growth
Chondrocytes»_space; _ AA uptake _ protein synthesis _ RNA & DNA synthesis _ collagen & chondroitin sulfate _ cell size & number
» _ linear growth
Mediate action of GH on chondrocytes & linear growth, pro- tein metabolism & organ size, and lean body mass
Polypeptide growth factors
Secreted by liver & other tissues
Somatomedins (Insulin-like Growth Factors I & II)
Types of Somatomedins (Insulin-like Growth Factors I & II)
IGF-I (Somatomedin C) - skeletal & cartilage growth
- Increases in parallel with GH _
- Both GH- & insulin-dependent _
- Lower in old age: angina pectoris, myocardial infarc- tion, atherosclerosis _
- Earlier death in aging men with low levels
IGF-II fetal growth regulator; increased by PRL _
GH & somatomedins can act both in cooperation and independently to stimulate pathways that lead to growth _
Factors that can STIMULATE GH SECRETION
DEC glucose, Stress (Hypoglycemia, Anesthesia, Surgery, Trauma, Infection, Fever, Exercise, Blood Extraction), NTs: Dopamine, Ach, Serotonin, Norepinephrine
Excessive activation of somatotropes or (+) acidophilic pituitary tumors
Excessive GH before puberty/ fusion of epiphyses with shaft
Gigantism - Rapid growth of all body tissues
Relate excessive GH results to Hyperglycemia
Eventual degeneration of overactive pancreas - DM development
Factors that can INHIBIT GH SECRETION
Somatostatin (INC Glucose, Free FA), Somatomedins, GH, Obesity, Cortisol, Pregnancy, Senescence
How is Growth Hormone Regulated?
(Long-term)
» Long-term nutritional state of tissues (protein nutrition level)
» Rate of GH secretion is increased by nutritional deficiency or excess tissue need for cellular proteins
»_space; Synthesis of new proteins & conserving existing ones
Management for Panhypopituitarism
Microsurgical tumor removal - Pituitary gland irradiation
Excessive GH after puberty / epiphyseal fusion with shaft
Acromegaly
Characteristics of Acromegaly
Thicker & enlarged bones
- Hands, feet
- Membranous bones (cranium, nose, forehead, supraor- bital 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
Joint deformities or frank arthritis
Secondary DM
Sleep apnea
Kyphosis
How is Acromegaly has INC coronary risk
Poor glucose tolerance
- Hypertension
- Lipid problems
Life of person with Acromegaly is shorter by average 10 years (vs. normal person), true or false?
TRUE
How is Acromegaly treated
Normalized by treatment of adenoma (surgery, oc-
treotide, radiation)
Growth Hormone Deficiency
If adult onset typically with other AP hormone deficiencies If childhood onset dwarfism
_ secretion of all AP hormones
May be congenital, slowly or suddenly develop
Panhypopituitarism
Causes of Panhypopituitarism
Causes:
- Pituitary tumor
- Suprasellar cysts
- Enlarged Rathkes pouch remnants
- Pituitary infarction & necrosis from post-partum hemor- rhage (Sheehan syndrome)
Manifestations of Panhypopituitarism:
Hypothyroidism (e.g., lethargy)
Depressed glucocorticoid production by adrenals (e.g., weight gain)
Suppressed gonadotropic hormone secretion (e.g., lost sexual function)
Most signs & symptoms treatable by adrenocortical & thy- roid hormones
Causes of (Pituitary) Dwarfism
Panhypopituitarism during childhood
- Hypothalamic dysfunction, GHRH deficiency
- Pituitary destruction, GH deficiency Isolated GH deficiency
- Biologically incompetent GH
- GH receptor deficiency
Unresponsive GH receptor (Laron dwarf/ GH insensitivity)
Hereditary inability to form somatomedin C (IGF-I) (Afri-
can pygmy; Levi-Lorain dwarf)
Manifestations of Dwarfism
Proportional body parts
- Short stature
- Greatly _ development rate
- Does not go through puberty
- Insufficient gonadotropic hormones for sexual matu- ration
- IfonlyGHdeficient(1/3)_maturesexually&repro- duce
Human GH synthesized by E. coli
if purely GH deficiency_completely treatable if given early
Dwarfism & replacement therapy in growth-deficient children
2nd X chromosome in females either absent or deformed _growth & development problems
Turner’s syndrome
Use of GH for HIV
To treat muscle wasting
Use of GH as Anti-aging
Increased protein deposition, esp. in muscles
_fatdeposits
Feeling of invigoration of energy
GH + exercise: _ type II muscle fibers in elderly
Use of GH as physical performance enhancer in SPORTS
Used for perceived anabolic effects on muscle growth & recovery (e.g., in weight lifting, body building, football, etc.)
- Combined with anabolic steroids, erythropoietin
- Studies: no _ muscle size or strength after hGH injection
Cells and Hormones in the Anterior Pituitary Gland
Corticotrope ACTH CRH Adrenal, Adipose,»_space; Cortisol
Somatotrope GH/Somatotropin GHRH,GHIH All tissues»_space; IGF-I
Gonadotrope FSH, LH GnRH Gonads»_space; Estrogen, Progesterone, Testosterone, Inhibibin
Lactotrope PRL PIH Breast, Gonads»_space; None
Thyrotrope TSH TRH Thyroid Gland»_space; Tri-iodothyronine
