Endocrinology 3 Pituitary BM Endocrinology 2011 Helen Christian The Pituitary How is the pituitary organised? Which hormones are produced? How are the hormones released? Where do the hormones act? Consequences of too much/too little hormone Pituitary location and MRI appearance Structure of the pituitary gland Posterior Anterior = neurohypophysis =adenohypophysis Ant Post 1
Development of the pituitary Organisation of the pituitary 5 weeks 20 weeks pituitary fossa transphenoidal surgery Organisation of the pituitary The discovery of hypothalmic control of the pituitary Median eminence Optic chiasm internal carotid branch Anterior pituitary neurosecretion Posterior pituitary jugular vein Geoffrey Harris 1913 1971 1977 Schally and Guillemin Nobel prize for identifying releasing factors 2
Anterior pituitary five endocrine cell types each secrete different hormone(s) Ultrastructure of anterior pituitary PRL ACTH cell types can be differentiated by antibody labelling and cell structure non-secretory supporting cell type folliculo-stellates capillary Fenestrated capillaries fenestrations Feedforward and feedback control -ve Hypothalamus inhibitory feedback Releasing hormone feedforward control -ve Anterior pituitary Trophic hormone capillary Endocrine gland Target e.g. cortisol release from the adrenal 3
The hypothalamic-pituitary-thyroid axis Inhibitory feedback TRH thyrotrophs anterior pituitary TSH thyroid T3 and T4 Thyrotrophin Releasing Hormone Thyroid Stimulating Hormone cold GPCRcAMP Pathology of TSH secretion is v rare Adrenocorticotrophic hormone (ACTH) Chemical type: polypeptide hormone from POMC precursor, secreted by corticotroph cells Receptor: G protein coupled receptor to camp Actions: stimulates secretion of cortisol (glucocorticoid hormone) from adrenal cortex in stress stimulates growth of adrenal cortex The hypothalamo-pituitary-adrenal axis Stress hypoglycaemia Diurnal rhythm of plasma ACTH and cortisol CRH Inhibitory feedback anterior pituitary corticotrophs ACTH adrenal cortex Corticotrophin Releasing Hormone ortisol co glucocorticoids, cortisol 4
ACTH pathology excess ACTH, and in turn excess glucocorticoid, - Cushing's disease deficiency of ACTH, in turn glucocorticoid deficient- Addison's disease.see adrenal lecture week 5 Gonadotrophins: LH and FSH Actions: reproduction Female: FSH follicle development and ovulation, LH synthesis of sex steroids by the ovary Male: LH controls testosterone production FSH stimulates sperm production Deficit: infertility in adult life lack of sexual maturation Excess: precocious puberty See Trinity term Reproduction lectures Hypothalamo-pituitary-gonadal axis -ve ovary GnRH estrogen anterior pituitary gonadotrophs LH + FSH testes LH = luteinising hormone FSH = follicle stimulating hormone Cyclical release in menstrual cyclecle testosterone Control of prolactin release anterior pituitary lactotrophs PRL Breast growth and milk production suckling +ve dopamine INHIBITORY tyrosine kinase enzyme -linked receptors Inhibits reproduction lactational amenorrhaea 5
Control of prolactin release Only pituitary hormone whose principal control is inhibitory PRL production is stimulated by estrogen during pregnancy Dopamine agonists e.g. bromocryptine, suppress lactation Pathology: prolactinomas hypersecrete PRL cause infertility and milk production Growth hormone axis Liver IGFs GHRH Hypothalamus Anterior pituitary somatotrophs GH Long bone and muscle growth GH -ve GH Enzymelinked receptors Growth hormone release is pulsatile GH pathology Gigantism due to excess GH secretion Short stature if lack GH nb if prior to epiphyseal plate fusion at puberty March 2010 Sultan Kosen 8ft 1 is the tallest man in the world and China s He Pingping the smallest at 2ft 5in. 6
Acromegaly Mutations in Aryl hydrocarbon-interacting protein predisposes to pituitary adenoma in childhood Due to excess GH secretion after epiphyseal plates have fused Enlargement of hands and feet Coarsening of facial features largening of nose Weight gain DNA extracted from the skeleton of a 7ft 7in patient b1761 kept in Hunterian museum, London. The same mutation was identified in 4 living N Ireland families who presented with gigantism. Pituitary tumours hormonal effects: hormone-secreting tumours effects depend on cell type mechanical effects: affects vision as presses on optic chiasm Posterior pituitary Formed by axons and terminals of hypothalamic neurosecretory neurons Secretes peptide hormones anti-diuretic hormone (ADH, also known as vasopressin) and oxytocin Ant Post Adenoma 7
Stimulus depolarises neuron Stimulation of posterior pituitary hormone release action potential : oxytocin and ADH produced in cell bodies axon Ca 2+ posterior pituitary exocytosis Antidiuretic hormone - ADH ( = vasopressin) Chemical type: Peptide 9 amino acids Receptors G protein coupled to camp Actions increases water reabsorption o in collecting ducts of kidney See Trinity term Kidney lectures Stimuli of ADH release Plasma osmolality Blood volume Diabetes insipidus Too little ADH function Two types: hypothalamic: lack of ADH production renal: lack of ADH action Brattleboro rat lacks ADH, drinks 70% of body weight per day, urinates constantly 8
Oxytocin Chemical nature: peptide Receptors: PLC-coupled Actions: contraction of uterine muscle in childbirth milk ejection by contraction of breast myoepithelium Control of oxytocin release stretch of cervix/vagina at parturition suckling nipple stimulation causes milk-ejection reflex Pathology deficit may cause prolonged labour knockout mice labour normal but no milk-ejection See Trinity term Reproduction lectures Pituitary : the master gland Endocrinology Week 1 General principles Week 1 Hormone action Week 2 Endocrine pancreas Week 3 Pituitary Week 4 Thyroid Week 5 Adrenal Week 6 Endocrinology Cells and Tissues Any questions email: helen.christian@dpag.ox.ac.uk 9