Growth Hormone & Somatomedin

Question 1

Somatotrophs comprise ~ _% of the hormone-producing cells of the anterior pituitary

Answer 1

50%

Secretes growth hormone

Question 2

Major physiological effects of GH

Answer 2

Stimulation of postnatal somatic growth & development

Modulation of metabolism in adults

Question 3

Regulation of GH pulsatile secretion

Answer 3

• Hypothalamic hormones:
  
  • Growth hormone-releasing hormone (GHRH)
    
    • ​Stimulates adenylyl cyclase and increases intracellular cAMP & Ca²⁺
  • Somatostatin / Somatotropin release-inhibiting factor (SRIF) inhibits
• ​IGF-1 / Somatomedin C
  
  • ​ inhibits GHRH
  • stimulates somatostatin

Question 4

Growth hormone therapy

Answer 4

higher mortality rate and higher risk of tumors

Question 5

The phospholipase C/ DAG/ IP3 and PKC pathways regulat eGH secretion how?

Answer 5

Increasing Ca²⁺

Activating PKC

Question 6

What hormones upregulate GH?

Answer 6

• Stress, sleep, aa-rich meal –> hypothalamic GHRH release
  
  • Short-term:
    
    • Increases cAMP, Ca²⁺, and IP₃
    • Increases somatotroph’s GH release
  • Long-term: increase GH transcription via Pit-1
• ​Thyroid hormone & cortisol synergistically enhance transcription
• Estrogen & testosterone mildly increase GH transription & synthesis in young adults

Question 7

Downregulation of GH synthesis & transcription

Answer 7

• GH & somatomedin induces somatostatin –> inhibit GH release
  
  • Somatostatin binds its own receptor to inhibit GH secretion by decreasing cAMP and Ca²⁺

Question 8

Describe the biological action of GH

Answer 8

• Anabolic & diabetogenic.
• Mediated directly AND indirectly through GH-stimulated production of IGF-1 by the liver and local nonliverproduction
• IGF-1 –> linear growth, organ size, lean body mass

Question 9

What impact does fasting have on GH & IGF-1?

Answer 9

Increase in GH (anabolic) will promote lipolysis because we now want to conserve glucose for essential tissue (e.g. brain) –> burn fat

Decrase glucose uptake by the muscle

Increase gluconeogenesis by liver

Question 10

When do GH level peak in fetal serum?

Do premature of full-term infants have higher serum GH?

When does GH peak in the lifetime?

Answer 10

20th wk of gestation

Premature infants have higher GH

Amt of GH secreted is greatest during adolescence, then decreases with age

Question 11

Somatostatin

aka

GH-inhibiting hormone

Answer 11

Hypothalamic peptide that diminishes the frq and amplitude of GHRH pulses

Does this by acting through its own membrane receptor –> decrease intracellular Ca²⁺ and cAMP

Question 12

GH release pattern is also influenced by

Answer 12

Question 13

What stimulates somatostatin (GHIH)?

Answer 13

Hyperglycemia

High FA

Question 14

How does [glucose] and [FA} impact GH?

Answer 14

A sharp drop in [glucose] or [FA}, such as in short-term fasting

–> increase plasma GH

Elevation of glucose or FFA, such as in obesity

–> reduces plasma GH

Question 15

How do deep vs light sleep impact GH?

How do various stresses (trauma, surgery, fever) impact GH?

Answer 15

Deeper sleep –> more GH

Stress increases plasma GH

Question 16

What do children who have GH deficiency look like?

What does GH replacement therapy cause?

Answer 16

Short & moderately obese

GH therapy

• enhances positive nitrogen balance
• decreases urea production
• redistributes fats
• reduces carbohydrate utilization

Question 17

Unlike other hormones, GH for humans must come from

Answer 17

other primates

(e.g. cant use pig like insulin

Question 18

mechanism of GH at the receptor

Answer 18

1. GH binds to JAK-STAT receptor dimer
   
   1. Intracellular domains dock and activate the JAK-STAT tyrosine kinase pathway
2. Activated JAK tyrosine kinases phposphorylate STAT transcription factors –> activates GH-dependent gene transcription and expression

Question 20

Somatomedins / IGFs

where do they originate? what are they produced in response to?

What happens if you have high GH but not IGF?

Answer 20

Produced in response to GH and are produced by many tissues, but mostly in the liver.

They mediate the typical GH responses, so not having IGFs –> retarded growth despite high GH

Question 21

How are IGF’s availability to tissues regulate?

Answer 21

They circulate bound to large binding proteins

Question 22

Both IGFs, but especially __, are greatly reduced in the plasma of GH-deficient subjects

Answer 22

IGF-1 is greatly reduecd in the plasma of GH-deficient subjects

Question 23

Describe IGF & GH levels in the fasting condition

Answer 23

High GH, low IGF

_{Because fasting -> low insulin, high GH -> IGFs activated neg feedbacks on itself to low IGF (but GH stays high in response to low IGF) ?}

Question 24

Locally-produced IGF-1 contributes to the stimulatory effects of GH, especially ____

Answer 24

enhancement of longitudinal growth

Question 25

GH & IGF in longitudinal growth of bones

Answer 25

**GH** --\> stimulate differentiation of prechondrocytes into early chondrocytes, which secrete IGF-1 **IGF** --\> stimulate clonal expansion and chondrocyte maturation

Question 26

**Administration of IGFs to GH-deficient** children or adults decreases has what impact on: * plasma amino acid levels * lean body mass * fat mass * bone formation * resting metabolic rate, exercise capacity, well-being

Answer 26

**amino acid lvls** decrease bc \*protein synthesis\* **lean body mass** INcrease & **fat mass** DEcreases **Bone formation** is enhanced **Metabolic rate, exercise capacity,** and **wellbeing** INcrease

Question 27

The most specific effect of GH is

Answer 27

**Acceleration of linear cartilage growth center growth in long bones** Cartilage-forming cells stimulated during **collagen & proteoglycan chondroitin synthesis**, which forms the ECM of cartilage

Question 28

Most specific tissues share in the **anabolic** response to GH

Answer 28

GH stimulates **DNA, RNA,** and **protein synthesis** in almost all cell types.

Question 29

GH & senescence

Answer 29

Decrease in GH with aging --\> less anabolic effects

Question 30

In what ways does **GH oppose the actions of insulin**?

Answer 30

* GH stimulates insulin gene expression, BUT it also induces **insulin** **resistance** * **Inhibits glucose uptake** by muscle & adipose cells --\> increase plasma glucose * **Enhances lipolysis** & opposes insulin's lipogenesis

Question 31

GH is a \_\_\_genic hormone

Answer 31

diabetogenic

Question 32

GH has what impact on **plasma free FA and ketoacids**? What about on **adipose tissue?**

Answer 32

**Increases** plasma fFA & ketoacids **Decreases** adipose tissue

Question 33

Acromegaly

Answer 33

Excessive GH secretion after puberty * Causes: pituitary tumor, hyperpituitarism, somatotroph tumors * Characteristics: * *Thick & oily skin,* esp face and scalp * *Delayed diagnosis*: often not diagnosed until 15-20yrs old

Question 34

Both **GH & insulin together augment** \_\_\_\_, leading to increased lean body mass. What is th**e purpose of insulin-antagonistic effect of GH**? What happens to **insulin, GH, and IGF during fasting**?

Answer 34

Together, they augment **IGF production** The insulin-anatagonistic effect of GH **prevents hypoglycemia** when you're fasting (dont want high insulin) *Fasting*: GH rises -\> inuslin falls -\> IGF declines

Question 35

Prolactin's structure is homologous to ___ and is synthesized as a \_\_\_. What happens to it in the ER? In the Golgi?

Answer 35

Homologous to **GH** ## Footnote Synthesized as a **preprohormone** Temporarily **N-glycosylated** in the ER **Deglycosylated** in the Golgi

Question 36

What form of prolactin is the major circulating form in NONpregnant women?

Answer 36

**Glycosylated prolactin** is constituvely secreted because it exhibits lower biological activity

Question 37

**Prolactin** secretion is regulated by

Answer 37

* Inhibited: * **Dopamine** * **Somatostatin** * _{GnRH (alternative form)} * Stimulated: **TRH**

Question 38

Biological effects of prolactin

Answer 38

* Breat development * Milk production * Reproductive function in both genders

Question 39

**Disruption of pituitary connections to hypothalamus** can have what impact on **prolactin secretion?**

Answer 39

**Increase** prolactin secretion

Question 40

Why does **excess prolactin** cause infertility in women and men?

Answer 40

**Excess prolactin inhibits GnRH release** --\> lack of ovulation, decreased sperm production

Question 41

\_\_ contributes to stimulation of parental protective behavior in newborns

Answer 41

prolactin