Lec 21 - Prolactin and GH

What parts of the pituitary gland does lactation require

Both anterior and posterior

- Anterior = prolactin

- Posterior = oxytocin

Where and what produces prolactin

Made by lactotrophs in anterior pituitary

Forms of prolactin in circulation

Monomer

Dimeric (big)

Macroprolactin -polymeric or immunoglobulin bound

Function of prolactin

- Pregnancy and lactation (breast milk production)

- uterine smooth muscle contractions

- Reproduction (sex hormone synthesis and fertility)

Specimen requirements and testing methods for prolactin

Serum or plasma (note TOC), tested via immunoassay

Gender variation of prolactin

Gender dependent - females secrete more than males

When are prolactin levels the highest

In the morning (pulsatile, diurnal variation)

Interferences of prolactin immunoassays

Non-specific immunoassays

Hook effect: high dose of antibody neutralizes ability for second Ab to do work = false neg (could be caused by MM)

Effect of dopamine on prolactin

Inhibits prolactin released

What causes increased secretion of prolactin

Suckling

Estrogen

Stress (severe illness, traumatic experience)

Thyrotropin releasing hormone (from the thalamus)

Physiological causes of hyperprolactinemia

Pregnancy, Breast feeding, stress, exercise, sleep

Non-physiological causes of hyperprolactinemia

- Prolactin secreting pituitary tumor

- Damage to hypothalamic pituitary dopamine path

- Medications

- Renal failure

- Liver disease

- Primary hypothyroidism (increased TRH)

- Macroprolactin

Clinical presentation

- Galactorrhea (breast discharge)

- Hypogonadism and infertility

- Low sex drive

- Headaches and visual problems

Hyperprolactinemia presentation in females

Menstrual dysfunction

Vaginal dryness

Hyperprolactinemia presentation in males

- ED

- Decreased body hair and muscle mass

- Delayed puberty

Diagnosis of hyperprolactinemia

Increased prolactin concentration in serum immnoassays

- if required, screen samples for macroprolactin (not bioavailable)

MRI - tumors

How to ID macroprolactin in samples

Gel filtration chromatography, PEG precipitation

Where is GH produced and secreted

Somatotrophic cells of anterior pituitary gland

What forms can be GH be found as

Monomer

Homodimer

Heterodimer

Multimer

GH distribution

50% Free, 50% bound to GH binding protein

Half life of Gh

20 mins - short

How is GH action mediated

Directly through growth hormone receptors on many tissues

Indirect action through hepatic insulin growth factor (IGF-1) release

Major functions of GH

- Tissue and bone growth

- Response to stress

- Modulates fat/carb/protein metabolism and body composition (decreases lipogenesis, increases lipolysis, amino acid uptake, glucose and protein synthesis)

- Raises glucose and FFA concentrations

What impacts amount of GH secretion

- Pulsatile release with most release at night

- Circadian rhythm

- Influenced by age, sex, body composition

- Measured via immunoassay

Is GH testing common?

No - mostly use Insulin-like growth factor

What criteria is required for GH to be ran instead of IGF-1

1. Patients with acromegaly being monitored for therapy

2. Pre-approved endocrinologists

3. Pediatric patients less than 1 year old

Positive influences on GH secretion

- Exercise

- Stress

- Sleep

- Fasting (hypoglycemia)

- AAs

- Hormones

- NTs

Negative influences on GH secretion

- Cortisol

- Hyperglycemia

- Obesity

- FFA

- Hypothyroidism

- Aging

- IGF-1: high amounts

Effect of GH on bone

Bone repair, stimulates osteoblasts

Effect of GH on Liver

Produces IGF-1

Effects of GH on fatty tissue

Promotes lipogenesis (FFAs for use)

Effect of GH on glycogen

Glycogenolysis - for sugar use

Where is IGF1 produced

Liver

Effect of IGF-1

Mediates indirect growth and fat metabolism effects of GH

Why is IGF a good marker for GH status

Fairly steady concentration throughout the day (good marker for GH status)

IGF reference ranges

Huge variation between and year

Causes of GH excess

Causes

- Pituitary tumors (adenoma)

- Hypothalamic lesions

- GnRH producing tumors

Effects of GH excess

Soft tissue, and bone overgrowth (gigantism in adults and acromegaly in adults)

Physicical features of kids with GH excess

Tall, long bones, large/coarse facial features

Physical features of adults with GH excess

- Large/coarse facial features

- Large organs

- Skin changes

- Osteoarthritis

- Hypertension

- Insulin resistance

Lab testing of GH excess

1. Measure serum IGF-1 (screen)

2. Glucose supression test (give glucose, measure serum GH 2 hours post dose, should make GH undetectable)

3. MRI for tumor

Should patients fast for glucose supression test

Yes

Causes of GH deficiency/resistance

Pituitary or hypothalamic abnormalities (deficiency)

GH insensitivity or resistance

Characteristic features in children with GH deficiency

- Low growth rate

- Short stature

- Central adiposity

- Susceptible to hypoglycemia

Characteristic features in adults with GH deficiency

- Decreased bone density

- Impaired serum lipids

- Abnormal body composition

- Premature mortality

Should you run glucose suppression test for GH deficiency?

No - only excess

GH deficiency lab testing

1. IGF-1 levels (screening)

2. Exercise stimulation test (20 min exercise should cause GH elevation)

3. Insulin tolerance test (give IV insulin - can be dangerous in patients!)

Theory of Insulin tolerance test

Insulin makes someone hypglycemic - GH should increase to return glucose levels to normal

Theory of glucose suppression test

Giving glucose should suppress GH release in body. Failure to suppress GH release indicates acromegaly

How to treat GH deficiency

Treat with GH supplements (recombinant hGH)

hGH misuse

Athletes will take hGH to increase lipolysis, lean muscle mass, VO2 max.

Can also take EPO