Endocrine 3 - Adenohypophysis, GH, Prolactin

Blood supply of the anterior pituitary

Superior hypophyseal artery - goes into the median eminence

Median eminence

Midline feature on the base of the brain marking the point at which the pituitary stalk exits the hypothalamus to connect to the pituitary. Allows for hypothalamic hormones to be transported to the anterior pituitary

hypothalamo-hypophyseal portal vessels

vessel traveling from the median eminence to the anterior pituitary lobe that carries hormones

Features of the Arcuate nucleus

Small cell bodies, short axons (parvocellular neurons)

Role of parvocellular neurons

Produce neural secretions that are released into blood vessels to anterior pituitary

Magnocellular neurons

Include the supraoptic nuclei and the paraventricular nuclei that secrete oxytocin and ADH to the posterior pituitary

Trophic hormone

a hormone that results in production of a second hormone in a target gland

Role of Gonadotropin releasing hormone (GnRH)

Stimulate FSH and LH production

Role of Growth hormone releasing hormone (GHRH)

Stimulate GH production

Role of thyrotropin releasing hormone (TRH)

Stimulate TSH and Prolactin secretion

Role of prolactin releasing factors (PRFs)

Stimulate prolactin secretion

Role of corticotropin releasing hormone (CRH)

Stimulate ACTH secretion

Somatotropin releasing inhibiting factor (SRIF)

Inhibits GH and TSH

Prolactin inhibitory factors (PIFs)

Inhibit TSH and PRL release

Most abundant PIF in the body

Dopamine

Role of TSH

Induces thyroid gland to release T3 and T4

Role of ACTH

Induces adrenal cortex to release cortisol

Role of Prolactin

Acts on mammary glands to stimulate milk secretion and breast growth

Role of GH

Acts on various tissues for intermediary metabolism, or acts on the liver to produce somatomedins (IGF-1), causing bone and soft tissue growth

Role of LH

Acts on gonads for sex hormone secretion (estrogen in women, testosterone in men)

Role of FSH

Acts on gonads for gamete production (sperm, ova)

general steps of negative feedback in hypothalamic anterior pituitary axis

1. Hypothalamus secretes hormone 1, that acts on anterior pituitary

2. Anterior pituitary releases hormone 2. This can act on target endocrine gland or cause negative feedback on hypothalamus (short loop)

3. Target endocrine gland releases hormone 3, which can act on target tissue or inhibit anterior pituitary and hypothalamus (long-loop negative feedback)

Role of GH on muscle

- Increased protein synthesis

- Decreased glucose uptake

- Anabolic = increased muscle mass

Role of GH on adipose tissue

- Decreased glucose uptake

- Increases lipolysis (increased blood FFAs)

- Decreased adiposity

Role of GH on the liver

- Increased protein synthesis

- Increased gluconeogenesis

- Increased somatomedin production (IGF-1)

What are the somatomedins

Insulin like growth factors: IGF-1, IGF-II

Effect of IGF-1

Effects bone chondrocytes

- Increased collagen synthesis

- Increased protein synthesis

- Increased cell proliferation

Increased linear growth

Effect of IGF-II

Effects many tissues and organs

- Increased protein synthesis

- Increased RNA synthesis

- Increased DNA synthesis

- Increased cell size, number

Increased tissue growth, increased organ size

Main regulators of GH secretion

Growth hormone inhibiting hormone (somatostatin)

Growth hormone releasing hormone

Somatomedins effect on the anterior pituitary, hypothalamus, and GH

Inhibitory effect

Positive regulators of GHRH secretion from hypothalamus

- Increased blood amino + fatty acids

- Deep sleep, exercise, stress, decreased blood glucose

Diurnal pattern of GH release (24H cycle)

Episodes increases in the dark and increased during sleep

GH release changes in response to blood nutrinet levels

- Fasting increases GH secretion

- Meals high in glucose and fatty acids suppress growth

- Meals high in amino acids increase GH

What cells synthesize GH

Somatotrophs

Secretion of GH

Episodic, more during stress/sleep

- Decreased due to age

- Reflects balance of GHRH and SRIF balance

GH deficiency in juveniles

Dwarfism

GH deficiency in adults

Somatopause (gradual and progressive decrease during age - similar to menopause)

Isolated GH deficiency (Type I dwarfism)

defect in GH production

Laron-type dwarfism

- Defect in GH action: GH receptor dysfunction

- Since GH cannot work, IGF-1 is low

Characteristics of GH deficiency in juveniles

Normal body proportions for age, no intellectual disability, mature sexually

Difference between GH dwarfs and hypothyroid dwarfs

Different body proportions

Somatopause

GH deficiency in adults

Impacts of somatopause

- Increased fat/ decreased lean mass

- Metabolic disturbances

- Impaired immune function (as GH drives immune system) - thymus is lost

How to treat somatopause

Exogenous hormone therapy (risky) - can induce gigantism or acromegaly

Effects of gigantism

Large organs

Issue with blood glucose management (diabetes)

Acromegaly

Excess GH production, causing increased size of face, hand, feet, jaw

- Internal organs can increase

- Increased glucose release = diabetes

Acromegalic features

- Large orbital ridges

- Broad, flat nose

- Large, fleshy lips

- Extensive spaces between teeth

- Thicky, oily, acne prone skin

- Prognathism (protruding jaw)

- Visual filed problems

- Osteoarthritic changes

- Hirsutism

- Large hands and feet

- Gynecomastia

Actions of prolactin

- Gonadal modulation (pro-gonadal when gonadal activity low, opposite when high)

- Mammary gland development

- Lactation (milk production)

Prolactin releasing factors

Thyrotropin releasing hormone (TRH)

Oxytocin (promotes milk let down)

Gonadal steroids that cause prolactin secretion

- Increase in testosterone or estrogen

- Progesterone decrease

Mammary stimulation that causes prolactin secretion

Suckling

Symptoms of hyperprolactinemia

Gonadal dysfunction, amenorrhea, reduced libido

Treatment of hyperprolactinemia

Dopamine agonist, tumor removal

Symptoms of hypoprolactinemia

Gonadal dysfunction, impaired lactation

Pituitary diabetes

Hypersecretion of GH, TSH - causes hyperglycemia

Hypopituitarism

Failure of pituitary gland to produce one or more of its hormones partially or completely

Panhypopituitarism

Inadequate or absent production of all anterior pituitary hormones