Terence (Endocrinology and the hypothalamic pituitary axis)

Question 1

Endocrinology

Answer 1

• Endocrinology is the study of hormones
• Classically hormones are chemical messengers secreted into the blood and exert their effect on a distal target
• Hormones exert their effects at low concentrations
• Hormones are important in maintaining homeostasis
• Hormones regulate many diverse functions including growth, development, metabolism, temperature, H2O balance, reproduction

Question 2

They hypothalamic pituitary axis

Answer 2

• Forms a complex functional unit that serves as a major link between the endocrine and nervous system.
• The hypothalamus is located below the thalamus and the pituitary gland is located below the hypothalamus in a bone socket at the base of the skull called the Sella Turcica. The sella tunica is part of the sphenoid bone.
• The hypothalamus synthesises neurohormones that regulate the endocrine activity of the pituitary gland or are released by the pituitary.
• The pituitary gland is often referred to as the master gland as it controls the function of many other endocrine glands and tissues

Question 3

The anterior pituitary

Answer 3

The hypothalamus secretes 7 different tropic hormones that act on other endocrine glands and control/stimulate the gland to synthesise/release a hormones from the anterior pituitary.
Connected via the hypophyseal portal system.
The anterior pituitary is a true endocrine organ. It synthesises and secretes hormones.

1. Neurons synthesising trophic hormones release them into capillaries of the portal vein
2. Portal vessels carry the trophic hormones directly to the anterior pituitary
3. Endocrine cells release their hormones into the second set of capillaries for distribution to the rest of the body

Question 4

Hypothalamus

Answer 4

The hypothalamus plays an important role is the synthesis and release of pituitary hormones. 7 of these regulate the synthesis and release of hormones from the anterior pituitary.

Question 5

Hypothalamic hormone- Thyrotropin releasing hormone

Answer 5

TRH is released from the hypothalamus and causes thyroid stimulating hormone (TSH) to be released from the anterior pituitary which then acts on the thyroid.

Question 6

Hypothalamic hormone- Prolactin release inhibiting hormone/dopamine

Answer 6

Prolactin release inhibiting hormone/dopamine is released from the hypothalamus and causes prolactin to be released from the anterior pituitary which then acts on the breast.

Question 7

Hypothalamic hormone- Gonadotropin releasing hormone

Answer 7

GnRH is released from the hypothalamus and causes FSH and LH to be released from the anterior pituitary which then acts on the gonads.

Question 8

Hypothalamic hormone- Growth hormone releasing hormone

Answer 8

GHRH is released from the hypothalamus and causes growth hormone (GH) to be released from the anterior pituitary which then acts on the liver/tissues

Question 9

Hypothalamic hormone- Growth hormone inhibiting hormone/ somatostatin

Answer 9

Growth hormone inhibiting hormone is released from the hypothalamus and causes growth hormone (GH) to be released from the anterior pituitary which then acts on the liver/tissues

Question 10

Hypothalamic hormone- Corticotropin releasing hormone

Answer 10

CRH is released from the hypothalamus and causes adrenocorticotropic hormone (ACTH) to be released from the anterior pituitary which then acts on the adrenal cortex

Question 11

Hypothalamic hormone- Prolactin releasing hormone

Answer 11

PRHis released from the hypothalamus and causes prolactin to be released from the anterior pituitary which then acts on the breast

Question 12

6 hormones synthesised and secreted from the anterior pituitary

Answer 12

TSH- Thyroid stimulating hormone- stimulated secretion of thyroid hormone from thyroid gland

ACTH- Adrenocorticotropic hormone- stimulates secretion of cortisol from the adrenal cortex

LH- Luteinising hormone- acts on gonads and stimulates production and secretion of sex hormones/ovulation

FSH- Follicle stimulating hormone- act on gonads and stimulates the development of egg and sperm and secretion of sex hormones

PRL- Prolactin- stimulates milk secretion

GH- Growth hormone- stimulates growth and energy metabolism (tropic as acts on liver to stimulate IGF1)

Question 13

Endocrine axis-driven feedback loop

Answer 13

This is where the hormone is regulated by the concentration of the hormone in the blood and not the response to the hormone.
Long loop- last hormone in pathway feedback to hypothalamus/anterior pituitary
Short loop- pituitary hormone feedback to hypothalamus

Question 14

The posterior pituitary

Answer 14

The posterior pituitary does not make hormones. It is not a true endocrine organ.
Neurones in the hypothalamus make 2 hormones
- oxytocin
- antidiuretic hormone (ADH)

These hormones are transported down nerve cell axons to the posterior pituitary and stored in the posterior pituitary until they are released (upon electrical stimulation) into the general circulation to act on distal targets.

1. Hormone is made and packaged in cell body of neuron
2. Vesicles are transported down the cell
3. Vesicles containing hormone are stored in posterior pituitary
4. Hormones are released into blood

Question 15

Hypothalamic hormone- Oxytocin

Answer 15

• Neuropeptide/hormone
• Controls uterine contractions during labour (positive feedback loop)
• Promotes milk flow in nursing mothers- the let down relflex
• Promotes bonding/social interaction
• Sometimes referred to as the ‘love hormone’

Question 16

Hypothalamic hormone- Anti-diuretic hormone (ADH)/vasopressin

Answer 16

• Acts on the kidneys
• Increases water reabsorption and thus regulates water balance in the body
• Promotes vasoconstriction and thus increases arterial blood pressure

Question 17

Oxytocin and childbirth

Answer 17

Baby pushing against the cervix causes activation of stretch receptors which causes nerve impulses from cervix to be transmitted to the brain. The brain stimulates pituitary gland to secrete oxytocin. Oxytocin is carried in the bloodstream to uterus and causes contraction of the smooth muscles of the uterus, pushing the baby further down the birth canal. This causes further activation of stress receptors and release of oxytocin. (positive feedback)
Upon birth, the stretching of the cervix halts, stopping the release of oxytocin.

Oxytocin can be given to:
- induce labour
- accelerate labour
- stop bleeding after delivery (routinely administered after Caesarean delivery)

Question 18

The let-down reflex

Answer 18

Suckling activates neurones which act on the hypothalamus to:
- increase oxytocin secretion
- decrease prolactin inhibitory hormone (acts to increase prolactin secretion)

Oxytocin acts on my-epithelial cells causing contraction which leads to milk ejection.
Prolactin acts on milk gland cells and stimulates milk synthesis.

Question 19

Antidiuretic hormone (ADH) deficiency

Answer 19

Diabetes Insipidus leads to increased blood sodium concentration, polyuria (excess urine production), and polydipsia (excess thirst).
The number of new cases of diabetes insipidus each year is 3 in 100,000. Usually starts in childhood or early adulthood.

Causes:
- Autoimmune destruction of cells and hypothalamus
- Genetics
- Damage to hypothalamus- injury/surgery

Diagnosis:
- Blood and urine tests
- MRI of the head and other tests might be done to look for an underlying cause

Treatment:
- ADH receptor agonists (e.g. Desmopressin)

Question 20

What causes an endocrine disorder?

Answer 20

An endocrine disorder is most often the result of a hormone imbalance, a condition characterised by a gland producing too much (hyperfunction) or too little (hypo function) of a hormone.
These are commonly caused by
- autoimmune disease
- endocrine tumour
- a genetic disorder
- injury to an endocrine gland

Question 21

Classification according to the origin of an endocrine disorder regulated by the hypothalamic pituitary system

Answer 21

Primary- the last step is impaired
- the cause of the disorder is in peripheral (target) endocrine gland

Secondary (or tertiary depending on which step further up is impaired)
- the cause of the hormonal secretions disorder is in the anterior pituitary to the hypothalamus

Question 22

Cortisol

Answer 22

Steroid hormone released from adrenal gland in response to stress (zona fasciculata of the adrenal cortex).

Increases blood glucose by:
- Promotes gluconeogenesis in liver
- Causes breakdown of skeletal muscle protein-providing substrates for gluconeogenesis
- Enhances lipolysis- providing fatty acids for other tissues
- Permissive effect only in presence of glucagon, synergistic effect in presence of glucagon and catecholamine

Suppresses the immune system- prevents cytokine release and antibody production. Hydrocortisol is used as an immunosuppressive drug.

Decreases plasma calcium- causes breakdown of bone and increases intestinal calcium absorption but increases calcium excretion resulting in a net loss of calcium.

Influences brain function- memory and mood.

Question 23

Hypercortisolism (over secretion of cortisol)- Cushing’s syndrome

Answer 23

Symptoms:
- Increased appetite and food intake- weight gain
- Increased fat deposits in face and trunk
- Immunosuppression
- Osteoporosis
- Hypoglycaemia
- Depression/difficulties with learning and memory

Causes:
- Tumour of the adrenal gland (primary hypersecretion), pituitary tumour or hypothalamus that secretes excess ACTH (secondary hypersecretion)
- Corticosteroid treatment for autoimmune disorders (Iatogenic cushings)
- Ectopic ACTH production (e.g. small cell carcinoma of the lung)

Question 24

Hypocortisolism (e.g. Addisons disease)

Answer 24

Symptoms
- muscle weakness and fatigue
- Weight loss and decreased appetite
- Darkening of the skin (hyperpigmentation)
- Low blood pressure, even fainting
- Salt craving
- Low blood sugar (hypoglycaemia)
- Nausea, diarrhoea or vomiting
- Muscle or joint pains
- Irritability/depression
- Body hair loss or sexual dysfunction in women

Causes
- Autoimmune destruction of adrenal cortex- primary hypofunction
- Rare genetic causes
- Exogenous cortisol leading to atrophy (cells that normally produce it stop and die)- need to carefully control cortisol treatment and removal of treatment