Endocrine system - axes and blood glucose

circadian/diurnal rhythm hormonal mechanism in relation to cortisol

CRH stimulates corticotrope cells to make and release adrenocorticotropic hormone (ACTH), which in turn stimulates cortisol release from the adrenal cortex. This raises plasma glucose levels. When cortisol concentration peaks long loop negative feedback is exerted on ACTH and CRH to decrease cortisol concentration and plasma glucose levels.

Circadian/diurnal pattern and negative feedback lag

There is lag in negative feedback due to the slow nature of endocrine signalling that allows cortisol levels to fluctuate throughout the day cycle. This results in a peak in cortisol levels early in the morning and a decline throughout the day.

The hypothalamopituitary complex

The hypothalamus responds to endocrine (hormonal) and / or neural stimuli by synthesising and secreting hypophysiotropic hormones. These act on the anterior pituitary gland via portal circulation to stimulate release of anterior pituitary hormones.

Portal circulation

A specialized blood vessel system that connects the hypothalamus and anterior pituitary, allowing for the direct delivery of hypophysiotropic hormones.

Neuroendocrine cells

Specialized neurons that produce small peptide hormones and secrete them into the bloodstream in response to neuronal signals, playing a crucial role in linking the nervous system and endocrine system, aka hypothalamic hormones.

posterior pituitary

Releases hormones with a lariat (lasso) structure stabilised by a cysteine disulfide bond known as oxytocin and vasopressin, which are synthesized in the hypothalamus and stored in the posterior pituitary before release into the bloodstream.

Fergusson reflex

a physiological response occurring during childbirth where the stretching of the cervix and uterine contractions trigger the release of the hormone oxytocin from the posterior pituitary gland. This release of oxytocin enhances the frequency and intensity of uterine contractions, promoting a more effective labor process. It is vital for the progression of labor, as it establishes a feedback loop that encourages further contractions until delivery occurs.

Hypothalamo-pituitary thyroid axis (HPT)

the hypothalamus releases Thyrotropin-releasing hormone (TRH) to stimulate the pituitary gland to secrete Thyroid-stimulating hormone (TSH), which then prompts the thyroid gland to produce thyroid hormones (T3 and T4) that negatively regulate metabolism by decreasing the metabolic rate.

RAAS

The Renin-Angiotensin-Aldosterone System (RAAS) controls blood pressure and fluid balance in the body. Less sodium detected by kidneys causes them to convert prorenin to the enzyme renin, which is secreted into the blood. Renin converts angiotensinogen to angiotensin 1 which constricts blood vessels increasing blood pressure. ACE converts angiotensin 1 to angiotensin 2 which binds to an AT2 receptor in the zona glomerulosa and stimulates aldosterone release which acts back on the kidney to promote sodium and water reabsorbtion and increase blood pressure.

HPA axis, ZF

the ZF synthesises glucocorticoids such as cortisol in response to adrenocorticotropic hormone (ACTH) released from the anterior pituitary. Cortisol is associated with chronic stress response and increases plasma glucose and non fatty acids, and inhibits the immune system to prioritise the function of vital organs. 3rd order feedback system (acts on anterior pituitary ACTH, hypothalamus CRH and metabolic input into the hypothalamus)

HPA axis, ZR

in response to stimulation from ACTH, the zr produces adrenal androgens such as dehydroepiandrosterone (DHEA), which are metabolised elsewhere to estrogen and testosterone. This is increased during puberty and decreases during later life.

Medulla

The inner section of the adrenal gland, consisting of chromaffin cells, which are derived from the neural crest. It produces catecholamines, such as epinephrine and norepinephrine, which are involved in the "fight or flight" response. (most norepinephrine is converted to epinephrine by PNMT which is upregulated by glucocorticoids from the zf) Adrenaline is stored in granules and released in response to neural input during the stress response

Adrenaline response

adrenaline acts on alpha and beta GPCR receptors. Alpha receptors increase intercellular calcium concentration, causing increased blood flow, blood pressure and heart rate while beta receptors activate adenyl cyclase action to increase cAMP levels and activate protein kinase A increasing blood glucose concentration. There is also sensitisation of the CNS such as pupil dilation and sweating.

islets of langerhan

in the pancreas, the alpha cells secrete glucagon, beta cells produce insulin, somatostatin secreted by delta cells functions locally to supress insulin and glucagon. pancreatic polypeptide secreted by pp cells for appetite control.

hypoglycaemia

a condition characterized by abnormally low blood glucose levels, often resulting in symptoms like dizziness, confusion, and sweating. causes brain function damage if sustained as brain function is only metabolised on glucose

hyperglycaemic

a condition characterized by abnormally high blood glucose levels, that affects water retention often leading to increased thirst, frequent urination, and fatigue. Glucose can stick to lipids and proteins causing long term kidney, nerve and capillary damage.

Blood glucose increase

Alpha cells repressed reducing glucagon synthesis. Beta cells activated causing insulin production causing an anabolic state of polymer synthesis

Blood glucose decrease

Beta cells repressed, decreasing insulin production; alpha cells activated leading to increased glucagon secretion, promoting gluconeogenesis (catabolic state) and maintaining blood glucose levels.

Beta cell insulin secretion

glucose enters the cell down a concentration gradient via a glut 2 transporter. This is converted by glucokinase to glucose 6 phosphate , maintaining the concentration gradient for further glucose uptake. glucose 6 kinase is used to synthesise atp in the tca cycle, which binds to and closes potassium channels causing depolarisation of the cell. This depolarization opens voltage-gated calcium channels, leading to an influx of calcium ions that triggers exocytosis of insulin-containing vesicles.

How food intake affects insulin secretion

food intake increases parasympathetic stimulation from stomach stretching. It also creates gastrointestinal hormones called incretins. both these signals increase insulin production.

insulin production and the stress response

sympathetic stimuli and adrenaline supress beta cells reducing insulin production. This response results in increased glucose availability for immediate use by tissues.

How cells respond to insulin

Insulin binds to a tyrosine kinase receptor, which cross -phosphorylates itself initiating a signalling cascade resulting in the excytosis of glut 4 into the membrane allowing increassed glucose uptake