Beyond the classic endocrine glands Flashcards
(19 cards)
Outline the pathophysiological mechanisms of ectoptic hormone production in relation to hormone-producing malignancies
- Cushing’s disease - ectopic ACTH production
- SIADH - tumour (non-osmotically)
- Heart
- Kidney
- Bone
- Tumours
- Pineal gland
What enzymes are contained in adipose tissue?
- Leptin - ⬆️ satiety
- Adiponectin - ⬆️ insulin sensitivity
- Androgens
- Can be metabolised in adipose tissue to form more active forms via aromatase for example
- Oestrogens
- Resistin
- Cytokines
Describe the function of apidocytes
Store energy as TGs, release energy as FFAs
LPL:
- TG hydrolysis (lipolysis) - Breakdown into FFAs + glycerol, happens at endothelial surface so FFA can be taken up by apidocytes, then esterified to new TG. When needed this can be hydrolysed inside apidocytes, forming FFA + glycerol
- Involved in receptor-mediated lipoprotein uptake
Hormone-sensitive lipase (HSL):
- When needed, fat stores as triacylglycerol (TG) is hydrolysed for energy use
Why can fat be considered an endocrine gland?
- Produces and releases hormones called adipocytokines:
- Leptin - Signals satiety to brain
- Adiponectin - Increases insulin sensitivity
- Resistin - Thought to be involved in development of insulin resistance and release of pro-inflammatory molecules
- Cytokines
- Androgens
- Oestrogens
Define metabolic syndrome
General disorder of energy metabolism associated with:
- Obesity (especially visceral)
- Hypertension
- Hyperglycaemia
- High serum TGs (but low HDL)
- Insulin resistance
Compare visceral and subcutaneous fat
Visceral (VS) and Subcutaneous (SC) express diff developmental genes, different signalling profiles. FFAs and apidocytokines released from VS fat drain directly to liver to alter metabolism
What are the incretin hormones?
- GIP - Inhibits gastric secretion and motility and potentiates release of insulin from beta cells in response to elevated blood glucose concentration - Stimulated by presence of fat and glucose in the small intestine
- GLP-1 - Potentiates insulin secretion in response to rising plasma glucose; reduces appetite - Stimulated by presence of glucose and other nutrients in the small intestine
What hormone from fat and the gut controls satiety? How can mutations with this lead to obesity?
Leptin:
- Mutations of leptin gene in adispose tissue or leptin receptor gene expressed in hypothalmaus lead to abnormal eating behaviour and development of early-onset morbid obesity.
- Obesity is associated with leptin resistance (leptin lvls already high in obesity)
What is the role of adiponectin?
Regulating metabolism and energy homeostasis:
- Primarily enhances insulin sensitivity
- Promotes breakdown of FAs for energy
- Anti-inflammatory protperties
What is the role of resistin?
Linked to development of insulin resistance and pro-inflammation which can also contribute to insulin resistance
Describe how healthy adipose tissue responds to leptin
- Leptin signals satiety to brain
- Adiponectin increases insulin sensitivity
- Resistin lvls low
Describe how adipose tissue in obesity responds to leptin
Obesity regarded as a state of chronic, low-lvl inflammation
- Leptin secretion high but resistance to leptin
- Adiponectin secretion low
- Insulin resistance, diabetes and metabolic syndrome
Cytokines (e.g. IL-6, TNF-alpha) - Normal balance disrupted
Cheokines (chemotactic cytokines) - Attract macrophages
How is food intake regulated?
- Hormones secreted from stomach and intestines
- Vagal afferents to the NTS
- Leptin secreted from apidocytes
All act on hypothalamus to alter appetite/food intake
Describe the appetite inhibitory pathways in the hypothalamus
- Increased food intake leads to secretion of leptin, insulin, PPY, Oxyntomodulin, GLP-1, CCK
- Stimulate POMC/CART neurones at ventromedial hypothalamus
- Hypothalamus secretes anorexigenic factors that inhibit food intake
Describe the appetite stimulatory pathways in the hypothalamus
During fasting/starvation:
- Increased ghrelin secretion, decreased leptin (ghrelin also stimulates GH secretion)
- Stimulates AGRP and NPY neurones at lateral hypothalamus
- Leads to secretion of orexigenic factors, stimulates food intake
What are circadian rhythms driven by?
The biological clock in the suprachiasmatic nucleus. Circadian rhythms not entrained to light dark cycle free run in excess of 24hrs
The suprachismatic nucleus sits just above the optic chiasm. It gets ligh input from special class of retinal ganglion cells, uses that to synchronise the biological clock to the night day cycle
In absence of sensory cues it generates its own rhythm.
Other rhythms respond to external daily cues
What rhythms are driven by the suprachiasmatic nucleus?
- Plasma melatonin - From Pineal gland
- Core body temp - ANS
- Plasma cortisol - From Adrenal gland
What is the function of the pineal gland?
Signals aboiut the level of light reach the pineal gland. Darkness is the signal that stimulates production and secretion of melatonin by the pineal, light inhibits it.
- Neural inputs to pineal from retina → SCN
- Superior cervical ganglion → Pineal gland
Synthesis of melatonin:
- L-tryptophan → serotonin → Melatonin
What are the endocrine functions of the kidney?
- Erythropoietin - Release in response to decreass tissue PO2, stimulates production of erythroctyes
- Vitamin D - Needed for calcium absorption, also endocrine function that converts vitamin D to active form
- RAAS
- Atrial natriuretic peptide
