L10 - Neuroendocrine Flashcards
!Describe a neuroendocrine cell
Specialised neurons embedded in capillaries (blood stream), where hormones (NT/NP) are released. It circulates and affects target tissues
T/F: Neuroendocrine peptides can be both hormones and NP
T
The distinction between NP and peptide hormone has to do with the cell types that release and respond to the molecule; NP are secreted from neuronal cells and signal to neighboring cells (primarily neurons). In contrast, peptide hormones are secreted from neuroendocrine cells and travel through the blood to distant tissues where they evoke a response.
Why do neuroendocrine peptides have limited usefulness as drugs? (4)
- Hard to make/purify
- Poor oral absorption
- Degraded rapidly by peptidases
- Non-peptide agonists/antagonists
Hypothalamus direct effect?
Releases hormones directly into blood via posterior pituitary – oxytocin and vasopressin
Hypothalamus indirect effect?
Releases hormones into portal hypophyseal circulation that act on anterior pituitary
Location of Hypothalamus and pituitary
- Base of brain, right next to the third ventricle
- Pituitary is below the hypothalamus
Oxytocin- function
- Baby crying -> oxytocin release -> milk letdown in mother
- Smooth muscle uterus contraction
Vasopressin - function
Released in response to reduction in blood volume or increase in plasma osmolarity, circulates to kidney
- increases water re absorption
- vasoconstriction
Hypothalamic indirect pathway
Neurons in Arcuate Nucleus projects to median eminence (an area leaky to BBB) then releases hypothalamic releasing factors/hormones into the hypohphyseal portal veins. These hormones circulate and binds to endocrine receptors in the anterior pituitary. This causes release of pituitary hormone in the blood which binds to a target organ. Another hormone is released – having more effects on the body.
Hypothalamic and anterior pituitary hormones are trophic – what does this mean?
Overproduction = hypertrophy of organs and hyperplasia
Underproduction = atrophy of organs
*Negative feedback regulates synthesis and release
Corticotropin Releasing Factor (CRF) releases which hormone?
- Adrenocorticotropic hornone
- alpha-mealanocyte stimulating hormone
- Beta-endorphin
Thyrotropin Releasing Hormone releases which hormone?
- Thyroid stimulating hormone
- Prolactin
What propetide synthesis increases with CRF?
POMC
HPA axis – ACTH synthesis and function
1) Activated by environmental/psychological stress
2) PVN axons project to hypophyseal portal veins to release CRF
3) Prohormone Convertase 1 (PC1) cleaves ACTH from POMC (CRF and Vasopressin promote synthesis of POMC)
4) CRF circulates and binds to anterior pituitary
5) Anterior pituitary releases ACTH that binds to melanocortin-2-receptors on adrenal cortex
6) This stimulates releases of GC – e.g. Cortisol
7) ACTH has negative feedback, inhibiting PVN and Ant. Pituitary
Cortisol is released in response to? Function?
- Released in response to stress and low blood-glucose concentration
- Increases blood sugar through gluconeogenesis
- Suppress the immune system (inflammation)
- Increases alertness and cognition
CRF1 Receptors
- GPCR
- Widely expressed, dominant receptor in brain and pituitary
- Endogenous agonist = CRF
CRF2 Receptors
- GPCR
- 3 Splice variants CRF2alpha/2beta/2gamma
- Endogenous agonist = Urocortin
CRF antagonists proposed as what kind of medication?
Anti-depressants and anxiolytics
ACTH can be cleaved to form? Why aren’t these formed in the corticotrophs?
Alpha-MSH and CLIP (unknown function currently). Corticotrophs don’t contain PC2 – but these can still be produced elsewhere in the pituitary
!Cushing syndrome – causes? Effect?
- Hyper secretion of ACTH caused by tumour
- Prolonged exogenous GC (e.g. prednisone or dexamethasone) treat inflammatory or autoimmune diseases
- Exogenous GC tends to be inhaled orally, hence effects aren’t as severe
-Effects: fat abs, thin arms and legs (muscle wasting), poor wound healing, osteoporosis, tendency hyperglycaemia
Growth Hormone (GH) – activates? How are defects treated?
- Activates GH receptors to induce IGF-1 synthesis and releases from the liver – increased protein synthesis and lipolysis
- Somatropin recomb prep used to treat growth defects
- High in newborn and declines after puberty
- Release is pulsatile
Somatostatin – what is it? What’s its analogue?
- HRF that inhibits release of GH from ant pituitary
- Octreotide – long acting analogue of somatostatin
- Used to treat gigantism in children (Excess GH pre-puberty)
- Treats acromegaly in adults (an excess prod of GF due to benign pituitary tumour – enlarged facial structures, hands and feet)
- Octreotide + surgery or radiotherapy to remove tumour
Hypothalamus receives 2 signals (regarding weight)
1) LT Adiposity signals: Leptin from adipose or Insulin from pancreas (these hormones circulate in our bloodstream proportional to our fat mass)
2) ST Satiety signals: liver, sympathetic input, vagus nerve input, CCK -> ultimately reaches NTS of medulla -> hypothalamus
What hormone is released by an empty stomach that will signal the brain? (This signal, unlike the others, doesn’t terminate when a meal is started– only stops when the stomach is stretched)
Ghrelin – the hunger hormone produced by GIT
