Lecture 81: AVP, oxytocin, growth hormones and pituitary

Which anatomical structure contributes to pituitary gland activity?

Hypothalamus

What are the 2 lobes of the pituitary gland and how do their functions differ?

Anterior lobe - synthesizes and secretes its own hormones

Posterior lobe - primarily stores and releases hormones produced by the hypothalamus

What four physiological changes are detected by the hypothalamus that stimulate vasopressin (ADH) release from the posterior pituitary?

1. Increased plasma osmolality (hyperosmolarity)

2. Decreased atrial receptor firing (↓ blood volume/pressure)

3. Increased angiotensin II

4. Increased sympathetic stimulation

Through which 2 mechanisms does vasopressin increase arterial pressure?

1. Activate V1 receptors causing vasoconstriction

2. Activate V2 receptors enhancing fluid reabsorption and increasing blood volume

What can reduced ADH levels lead to and how is this treated?

Can lead to diabetes insipidus, characterized by copious dilute urine

Treated with desmopressin (V2 agonist)

What can excess ADH (SIADH) levels lead to and how is this treated?

Syndrome where the body releases too much ADH

Lead to hyponatraemia (low sodium) or oedema

Treatment includes demeclocycline or tolvaptan

What is oxytocin?

Hormone involved in uterine contractions during labour and milk ejection during breastfeeding

When might oxytocin be administered?

Can be administered to induce labour (slow IV infusion via pump) or prevent postpartum hemorrhage

What are the two primary mechanical stimuli that trigger the release of oxytocin?

Stretch of the uterus/cervix and nipple stimulation

Which oxytocin antagonist is used clinically to manage pre-term labour?

Atosiban

What are the 2 groups of hormones in which the anterior pituitary lobe produces?

Tropic pituitary hormones and direct acting pituitary hormones

What are tropic pituitary hormones?

Any of a class of hormones from the anterior pituitary gland that affects the secretion of other endocrine glands (i.e have other endocrine glands as their target)

What are some examples of tropic pituitary hormones?

Adrenocorticotropic hormone (corticotropin), FSH and LH, and thyrotropin (thyroid-stimulating hormone)

What are some examples of direct acting pituitary hormones?

Growth hormone (somatotropin) and prolactin

Which hormones are released by the anterior and posterior pituitary gland lobes?

Anterior - growth hormone, prolactin, gonadotropins, ACTH

Posterior - oxytocin, antidiuretic hormone (ADH)

What is antidiuretic hormone (ADH) and what does it do?

Aka vasopressin, regulates renal function and water balance in the body

In the hypothalamic-pituitary-thyroid (HPT) axis, which two hormones exert negative feedback to regulate metabolism?

T3 and T4

What are the FSH effects in females and males?

Female: maturation of ovarian follicle

Male: supports sperm cell maturation

Growth Hormone (GH) secretion is inhibited by which hypothalamic factor?

GHRIF (Somatostatin)

What are the direct effects of growth hormone production from the pituitary gland?

Increased triglyceride breakdown

Increased protein synthesis

Gluconeogenesis

What are the effects of insulin-like growth factors (somatomedins) in the hypothalamic-pituitary-somatic (HPS) axis?

Stimulate bone and muscle growth

Metabolic effects

What are high levels of growth hormones secreted in response to?

Exercise, stress, sleep, thyroid hormones

How does noradrenergic activation via a β-antagonist affect GH levels compared to α-antagonist?

β-antagonist promotes secretion and α-antagonist inhibits secretion

Why may a patient be deficient in GH function?

Reduced secretion or receptor defects

What is the typical clinical manifestation of GH deficiency in children and adults?

Children : growth reduction/ dwarfism

Adult: increased body fat, decreased muscle and bone mass

Which recombinant form of human growth hormone is used to treat growth deficiency in children?

Somatropin, an SC injection

Only initiated by a specialist

What is gigantism?

A disorder due to excess growth hormone in childhood before the growth plates have closed

Leads to excessive linear growth → very tall stature

What is acromegaly?

A disorder caused by excess growth hormone (GH) in adulthood, after the epiphyseal (growth plates) have closed

Causes thickening of bones and soft tissues, not increased height

Which metabolic condition is a common consequence of the overgrowth of bone and connective tissue in acromegaly?

Glucose intolerance

Why is the dopamine agonist Bromocriptine used in the treatment of acromegaly?

Dopamine suppresses the hypersecretion of GH

Which somatostatin (GHRIF) analogue is used to reduce the amount of GH being secreted in acromegaly?

Octreotide

What are the consequences of GH counter-regulating glucose?

Has hyperglycaemic action and can cause insulin resistance

Which hormone is the primary inhibitor of prolactin release?

Dopamine

What is the most common hormonal disturbance of the pituitary gland?

Hyperprolactinaemia - suppresses reproductive hormones

What are the symptoms of hyperprolactinaemia?

Galactorrhoea, gynaecomastia (enlarged male breasts), infertility, amenorrhoea (no menstruation), erectile dysfunction, osteoporosis

What term describes the inappropriate production of milk in females or males due to high prolactin levels?

Galactorrhoea

What can cause hyperprolactinaemia?

Pregnancy, breastfeeding, stress, drugs (metoclopramide, haloperidol, oestrogen, antipsychotics), tumour secreting prolactin

What are the treatment options for hyperprolactinaemia?

Surgical removal of tumour

Bromocriptine (dopamine agonist)

Cabergoline (alternative dopamine agonist)

What is hypopituitarism?

Reduced secretion of anterior pituitary hormones

Affected in the following order: GH, FSH, LH, prolactin, TSH, ACTH

What is panhypopituitarism and what is this caused by?

Deficiency of all anterior hormones

Caused by irradiation, surgery, pituitary tumour

According to the HPS axis, where are Somatomedins (IGFs) primarily produced?

Liver

What is the primary effect of oxytocin on the uterus during labour?

It increases the frequency and strength of contractions

What is the target and effect of adrenocorticotropic hormone (ACTH)?

Target = adrenal glands

Effect = stimulates production of cortisol which regulate metabolism and stress response

What is the target and effect of thyrotropin?

Target = thyroid gland

Effect = stimulates release of thyroid hormones which regulate metabolism

What is the target and effect of growth hormone (somatotropin)?

Target = liver, bone, muscles

Effect = induce production of insulin like growth factors which stimulate body growth and higher metabolic rate