Pituitary hormones and ADHCan you describe the anatomy of the pituitary? Located at the base of the brain in the pituitary fossa (sella turcica) of the sphenoid

bone, below the optic chiasm Comprises 3 lobes: anterior, posterior, intermediate (not well developed in humans) Connected superiorly to the hypothalamus by the pituitary stalk Cells include chromophils (acidophils and basophils) and chromophobes (inactive)

What is the embryological derivation of the pituitary? Anterior: originate from an up-growth (Rathke’s pouch) of the mouth ectoderm Posterior: originate from a down-growth of the hypothalamus

What is the significance? Hypothalamus is linked to the anterior pituitary via hormones released into the portal

system Posterior pituitary consists of axon endings from the supraoptic and paraventricular

nuclei of the hypothalamus

What is a portal circulation?Arrangement by which blood collected from one set of capillaries passes through a large vessel to another set of capillaries before returning to the systemic circulation

What hormones are secreted from the pituitary? Anterior (FLAT PIG!)

o FSHo LHo ACTHo TSHo Prolactino GH

Posterioro ADHo Oxytocin

What does the intermediate lobe secrete?Releases melanocyte-stimulating hormones, regulating skin pigmentation

What controls their secretion?Three levels of negative feedback… Long-loop: peripherally produced hormones → hypothalamus and anterior pituitary Short-loop: anterior pituitary hormones → hypothalamus Ultra-short-loop: hypothalamic hormones → hypothalamus

What are their actions?Hormone Chemistry Actions ControlAnterior pituitaryFSH and LH Glycoprotein LH stimulates ovulation and the final maturation

of the ovarian follicles in the female and testosterone secretion in the male

FSH stimulates the development of ovarian follicles and regulates spermatogenesis in the testes

Stimulated by gonadotrophin-releasing hormone

ACTH Polypeptide Synthesis and release of glucocorticoids from the adrenal cortex

Stimulated by corticotrophin-releasing hormone, which is in turn controlled by the limbic system and is increased by stress

Inhibited by negative feedback from glucocorticoidsTSH Glycoprotein Stimulation of thyroid hormone synthesis Stimulated by thyrotrophin-releasing hormone

Inhibited by negative feedback from thyroid hormonesProlactin Polypeptide Development of mammary glands

Milk production Suppresses LH, causing amenorrhoea

Tonic inhibitory control by prolactin-inhibiting hormone (dopamine)

Stimulated by pregnancy and suckling Prolactin acts in the hypothalamus in a negative feedback

fashion to inhibit its own secretionGrowth hormone (GH)

Polypeptide Indirect: via insulin-like growth factors (somatomedins) from the liver Proteins:

o ↑ transport of amino acids into cellso ↑ protein synthesis

Fats:o Mobilisation of fatty acidso ↑ formation of acetyl CoA, so that fat is

preferentially used as an energy sourceo Excess GH can → ketoacidosis

Stimulationo Growth hormone releasing hormoneo Diurnal: more during sleepo Hypoglycaemiao Stress

Inhibitiono Somatostatin (from the hypothalamus)o Somatomedins (negative feedback)

Hormone Chemistry Actions Control Carbohydrate:

o ↑ hepatic gluconeogenesis and ↓ transport of glucose into cells, resulting in a diabetogenic (anti-insulin) effect

Bones:o Proliferation of osteoblasts →

epiphyseal growth, or periosteal growth if the epiphyses have fused

o ↑ cartilage growthPosterior pituitaryAntidiuretic hormone

Nonapeptide Stimulates water reabsorption Stimulates urea reabsorption, maintaining the

high medullary osmolality

Changes in osmotic concentration (>1% from set point of 285 mOsm/kg H2O)

Hypovolaemia (>10%) Angiotensin II Pain, stress, emotion and exercise N&V StandingSensitivity of the baroreceptor mechanism is less than that of the osmoreceptors, however volume stimuli override the osmotic regulation, allowing the kidney to conserve water during hypovolaemia

Oxytocin Nonapeptide Contraction of the mammary gland myoepithelium, resulting in milk ejection

Uterine contraction

Suckling

Tell me about thyroid hormones Thyroid hormones are amino acids containing iodine Include:

o Thyroxine (T4) primarilyo Tri-iotothyronine (T3), more activeo Reverse T3, not active

Mechanismo T4 deiodinated to T3o Binds to nuclear receptorso Initiates gene transcription, producing mRNAo mRNA is translated in the ribosomes, producing proteinso Therefore works slowly and has a long duration of action

Effectso Hormonal: negative feedback, ↑ insulin, glucagon, PTH, glucocorticoidso Metabolic:

↑ BMR via stimulation of Na+/K+ ATPase Carbohydrates: ↑ metabolism (uptake, glycolysis, gluconeogenesis, GI

absorption, insulin secretion) Fats: ↑ (mobilisation → ↑ FFAs but ↓ cholesterol, phospholipids and

triglycerides) Protein: variable (physiological → anabolic, large amounts → catabolic) Vitamins: ↑ requirements

o Growth: brain and boneo CV: inotropic, chronotropic, vasodilation → ↓ diastolic pressure and ↑ pulse

pressure (but MAP unchanged!)o Respiratory: ↑ metabolic rate → ↑ RR and tidal volume → ↑ minute ventilationo GI: ↑ secretions and motility, ↑ appetiteo Muscle: stimulates contractility but too much → catabolism → weakness o Sexual: oligomenorrhoea

Where are the hypothalamic osmoreceptors?Subfornical Organ and the Organum vasculosum of the lamina terminalis

Are they within or without the BBB? Their vascular supply lacks the typical blood-brain barrier Therefore, ions can cross between the blood and the interstitium This allows the osmoreceptors to rapidly respond to changes in ECF osmolarity, allowing

control over ADH secretion and over thirst

Tell me about the production, transport and secretion of ADH (See above table for more information)

Participates in a negative feedback loop to regulate osmolality

What are the effects in the kidney? Stimulates water reabsorption by increasing the water permeability of the collecting

duct membrane Activates V2 receptors on the basolateral membrane of principal cells in the collecting

duct (Gs protein coupled) → water reabsorptiono Via the second messenger cAMP, inserts aquaporin 2 water channels into the

luminal membrane

Stimulates urea reabsorption from the medullary collecting ducts, maintaining the high medullary osmolality

Effects:o ↓ ADH levels → water lost in excess of solutes → large volume of hypoosmotic

(dilute) urine is excreted → ↑ plasma osmolalityo ↑ ADH levels → water conserved in excess of solutes → small volume of

hyperosmotic (concentrated) urine is excreted → ↓ plasma osmolality

What are the vasopressin receptors? Are the second messengers in the vasculature the same as in the kidney?Receptor

Mechanism Function

V1a Gq Vasoconstriction: especially splanchnic and coronaryPlatelet aggregationHepatic glycogenolysisNeurotransmission in the brain and spinal cord

V1b Gq ACTH release from anterior pituitaryV2 Gs Antidiuretic

Factor VIII release from endothelium

What are the effects in the splanchnic system? Vasoconstriction

What are the effects on the lung? Vasodilation

How is it metabolised? Rapidly inactivated by peptidases in liver and kidneys (biologic t1/2 = 20 minutes)

Are there any hormones that inhibit its secretion? ANP GABA Opioids