BIOM2010 (till mid sem) Endocrinology. e.g. anterior pituitary gland, thyroid, adrenal. Pineal Heart GI Female

Transcription

1 BIOM2010 (till mid sem) Endocrinology Endocrine system Endocrine gland : a that acts by directly into the which then to other parts of the body to act on (cells, tissues, organs) : found at e.g. anterior pituitary gland, thyroid, adrenal Major endocrine organs Pineal Heart GI Female Hypothalamus Adrenal gland Liver Ovaries Pituitary Kidney Stomach Placenta (pregnant) Thyroid Adipose tissue Duodenum Male Parathyroid Skin Pancreas Testes Hormones

2 Physiologic response Hormone bound to, hormone response in liver or other tissues Excretion in Hormone action on target cells 1. or no receptor present 2. Modification to receptor so it doesn t activate signalling cascade 3. Downregulation of a component of signalling pathway Upregulation of an inhibitor of signalling pathway 4. Binding with receptor 1. Alters by acting on / 2. Acts through to alter activity of +/- 3. Activates to cause formation of

3 Hormone action on target cells intracellular signalling pathways (signal transduction) 1. e.g. OT, GNRH, somatostatin, DA receptors 2. e.g. insulin, IGF1 receptor 3. e.g. EPO, leptin, prolactin & GH receptors 4. e.g. oestrogen receptor Homeostasis : the state of of the body that is maintained by of &. Involves both the & systems. Negative feedback Positive feedback : : Endocrine Disorders Hormone activity Hyposecretion Hypersecretion Clearance Other

4 Pituitary Posterior pituitary Anterior pituitary Neural Blood borne Cell types 5 Hormones released 6 PVN SON Releasing & inhibiting hormones Posterior pituitary gland 1. - VP ( ) 2. - OT Neurons - One neuron express ONLY type of peptide (VP/OT) - Project to the 1. (SON) 2. (PVN) Hormones VP OT Actions Parturition: Lactation: Secretion Regulation Stimulation Inhibition Target cells

5 Oxytocin Synthesis Secretion MOA Regulation In males Class Compound Receptor Pathway Effects Oxytocics Oxytocin Tocolytics Atosiban Facilitates

6 Anterior pituitary gland Cell type Hormone Grouping Have direct effect in their own right Trophic hormones Function : Regulation of other tissues Hypothalamus Pituitary Axes e.g. (HPA axis) activity of each cell type is regulated independently of the others Stalk Section Hypothalamo-pituitary disconnection RF RIF RF RIF Prolactin Prolactin? GH GH TSH TSH ACTH ACTH? FSH & LH FSH & LH

7 Median eminence Hypothalamic-hypophyseal portal system Fenestra Portal veins Pituitary stalk Secretion control Response to neurohormones called From hypothalamus Releasing factors Structure Often Secretion Transportation From into at specialised region of hypothalamus In to a in the anterior pituitary gland.

8 Prolactin Growth hormone Structure Synthesis & secretion - Prolactin inhibiting factor (PIF) Short term response Medium term response Long term response Receptor - Expressed by - Signals via multiple pathways to suppress PRL - Inhibiting factor Females Males Amplitude Frequency Pulse Peak in 24 hour: Action - Prolactin releasing factor (PRF) - PRL synthesis Reproductive role Stimulates to & of e.g. milk proteins Non-reproductive role e.g., - Releasing factor Major determinant of growth Generally - no. & size in cells in e.g. skeletal muscles - thickness & length of distinct from effects of growth

9 Disorders Hyposecretion PRL Hypersecretion Female - Male GH Adult Adult No major Sx e.g. thyroid tumour 1. Enlarged - Bones in, & 2. Thickening leads to Children Children Body proportion: Body proportion: Stature: max. m Abnormally tall: m Muscle development: also affected Subcutaneous fat: - Diagnosed before puberty - Gives near normal growth

10 Somatomedin Hypothesis Growth Not weight gain alone Involves - Net synthesis - Lengthening of - cell ( ) & ( ) Growth curves : 2 major growth spurts Control of growth & metabolism Role of circulating IGF from liver Relative contributions from tissues other than liver

11 Pit1 is necessary for & GHRH +/- somatostatin GH Growth Plate Closure - Occurs after - Due to action - GH/IGF1 cannot cause further growth in bones (but can of bones) Epiphyses GH action Growing person / child (anti-insulin effect) - (anti-insulin effect) - Adult Growth Drug 1. (GHRH agonist) - Use test growth axis 2. (rhigf1) - For growth defects 3. (somatostatin analogue) - Inhibit GH excess : for acromegaly & gigantism - Inhibits other hormones producing tumours 4. - Similar to octreotide - Used for tumours

12 Endocrine pancreas 1. Carbohydrate (4.1 kcal/g) 2. Lipid (9.4 kcal/g) 3. Protein (4.3 kcal/g) Glucose - Important for all cells - Main energy source for - Neurones cannot store (glia can) are essentials for normal CNS function Glucose homeostasis blood glucose GI tract Liver hepatic blood glucose Transport of glucose into cells - - As through As Kidney - - Facilitated diffusion 1. Carrier protein takes conformation in which solute binding site is exposed to region of high concentration 2. Solute molecule binds to carrier protein 3. Carrier protein changes conformation so that binding site is exposed to region of lower concentration 4. Transported solute is released & carrier protein returns to conformation in step 1

13 GLUT Name Tissue Insulin sensitive Comments Hyperglycaemia Hypoglycaemia Signs of diabetes mellitus e.g. osmotic diuresis Insulin & glucagon Simple control system

14 Insulin Glucagon Islet of Langerhans Homeostasis Glucose, fatty acids & a.a. Impairment Receptor CHO Fats Proteins

15 Characteristics Type I Type II Descriptions Onset Insulin dependency Speed development Sx Tx Drugs 1. Insulin Tx for 1. (sometimes) 2. Emergency tx for 3. diabetes MOA: acts like Administration: (or ) Duration action: different for different formulations

16 Oral hypoglycaemics e.g. Biguanides Sulfonylureas Thiazolidinediones (glitazones) MOA SE 1. Repaglinide - Act like - Block cells 2. Acarbose - Reduces in GIT - Reduces increase during absorption