Hypothalamic-Pituitary Axis 2 Flashcards
Chemistry and physiology of somatotropes (GH)
- single chain 191 amino acids
- regulated by GHRH (+) and GHIH (-)
- stimulates body growth and insulin-like growth factor 1 (skeletal effects = increase cartilage and skeletal growth, extraskeletal effects = increase in protein synthesis and cell growth and proliferation)
- stimulates lipolysis
- inhibits actions of insulin on carbohydrate and lipid metabolism
Chemistry and physiological action of corticotropes (ACTH)
- single chain 39 amino acids
- regulated by CRH
- stimulates production of glucocorticoids and androgens by the adrenal cortex
- maintains size of zona fasciculata and zona reticularis of the cortex
Chemistry and physiological action of thyrotropes (TSH)
- glycoprotein of 2 subunits; alpha (89 amino acids) and beta (112 amino acids)
- regulated by TRH
- stimulates production of thyroid hormones by thyroid follicle cells
- maintains size of follicular cells
Chemistry and physiological action of gonadotropes (FSH, LH)
- composed of heterodimers of same alpha subunit (89 amino acids) but hormone specific beta unit (FSH = 112 amino acids, LH = 115 amino acids)
- regulated by GnRH
FSH: stimulates development of ovarian follicles, regulates spermatogenesis in testes
LH: causes ovulation and forms corpus luteum in ovary, produces oestrogen and progesterone in the overy, stimulates testosterone production in the testes
Chemistry and physiological action of lactotropes (prolactin)
- single chain 198 amino acids
- regulated by PIH (dopamine)
- milk secretion and production
Name the locations in the thalamus that neurohormones are released
paraventricular hypothalamus nucleus: TRH, GHIH, OXT, VP, CRH
periventricular hypothalamic nucleus: PIH, GHIH
arcuate hypothalamic nucleus: GHRH, PIH
preoptic area: GnRH
supraoptic nucleus: OXT, VP
Describe the regulation of the release of GH from the anterior pituitary gland by GHRH
- regulated by neurohormones from hypothalamus
- somatotropes respond to GHRH to release GH
- GHRH binds to g-coupled receptor causing a conformational change promoting interaction with G-protein (causing subunits to displace activating it)
- activates a membrane cascade activating adenylase cyclase leading to productionof cAMP which activates PKA which phosphorylates a membrane calcium channel to cause an influx of calcium into the cell
- this results in depolarisation of the cell causing exocytosis of GH from the cell
Describe the regulation of the release of GH from the anterior pituitary gland by GHIH
- inhibit release of GH by binding to SS receptor on the membrane
- causes recruitment of inhibitory g-protein
- interacts with adenylate cyclase to inhibit it which suppresses cAMP and therefore does not activate PKA
- no release of GH
Describe the regulation of GH release by feedback inhibition
- negative feedback sent from target tissue to level to anterior pituitary (short loop) as well as to the hypothalamus (long loop)
- IGF-1 directly inhibits somatotrophs in anterior pituitary and indirectly inhibits GHRH in hypothalamus
- also increases GHIH secretion from periventricular region
What happens when GH is deficient?
- dwarfism in children due to effects on bone growth and decreased availability of lipids and glucose for energy
- can be treated with recombinant GH therapy
What happens when GH is in excess (acromegaly)?
Before puberty: gigantism due to excess stimulation of epiphyseal plates
After puberty: no stimulation of linear bone growth due to fusion of epiphyses
- periosteal bone growth causing enlarged hands, jaw and feet
- soft tissue growth causing enlargement of tongue and coarsening of facial features
- insulin resistance and glucose intolerance (diabetes)
- treated with synthetic long-acting somatostatins (octreotide) until transphenoidal surgery
What are some common effects of acromegaly?
- amenorrhoea in women
- arthalgia
- hyperhidrosis
- sleep apnoea
headaches
Describe how AVP of the posterior pituitary is processed
- the precursor contains signal peptides to allow for packaging into secretory vesicles which helps direct it to correct cellular compartment
- recognised by ER protein which takes precursor protein as it is being synthesised by ribosome into ER and then the signal peptide is cleaved off
- precursor now pro-vasopressin
- inside secretory vesicles, enzyme cleaves AVP to make it functional and processes the rest of the protein
- section adjacent to AVP is neurophysin II which acts to stabilise and protect AVP in circulation prolonging its half life
- dissociates from AVP once it reaches its target tissue
- last section is copeptin which is secreted into circulation but is non-functional (can be used as surrogate for AVP)
Describe how oxytocin of the posterior pituitary is processed
- contains signal peptide to direct it to the correct compartment for packaging into secretory vesicles
- functional oxytocin is cleaved off
- other protein is neurophysin I (stabilises and protects oxytocin and prolongs its half life in circulation)
- dissociates from oxytocin once it reaches its target tissue
Describe the actions that AVP/ADH has on the body
Responds to:
- increases in blood osmolality (brain osmoreceptors)
- decreased blood volume (carotid/aorta/atrium)
- RAAS
Causes:
- recruitment of AQP channels to cause water retention in kidney
