The endocrine system Zsuzsanna Tóth, PhD Semmelweis University, Dept. of Anatomy, Histology and Embryology The role of the autonomic nervous system Claude Bernard • „milieu intérieur” concept; every organism lives in its internal environment that is constant and independent form the external environment Walter Bradford Cannon homeostasis; • an extension of the “milieu interieur” concept • consistence in an open system requires mechanisms that act to maintain that consistency • steady‐state conditions require that any tendency toward change automatically meets with factors that resist that change • regulating systems that determine the homeostatic state : o autonomic nervous system ( sympathetic, parasympathetic, enteral) o endocrine system Positive feedback + Disrupted sleep, Fatigue: disabled increases fatigue stress coping Stress, disrupted + sleep + Negative feedback Body temperature ↑ + Body sweets more ‐ feedback Homeostatic integration within the hypothalamus Endocrine system Not all endocrine glands are under hypothalamic control. The endocrine system Classic endocrine organs Pituitary gland (hypophysis) Pajzsmirigy, Thyroid and Thyroid and mellékpajzsmirigy Parathyroid glands Pineal gland Parathyroid glands Adrenal gland Pancreas: Testicles Islets of Ovaries Langerhans Endocrine gland: • Epithelial origin (except the adrenal medulla) • No excretory ducts, unlike in the exocrine glands (i. e. salivary gland) • Lobes, and lobules, separated by connective tissue septa • Hormone release into the bloodstream • Special, fenestrated capillary network Types of capillaries continous endothel Fenestrated endothel fenestra In endocrine organs The diffuse endocrine system organ example effect atrium of the heart atrial natriuretic peptide reduces the extracellular fluid (ECF) volume by increasing renal sodium (ANP) excretion enteroendocrine cells Cholecystokinin (CCK) increases production and release of in the gut bile from the gallbladder, hunger suppressant kidney renin blood pressure regulation‐RAS system liver hepcidin reduces of iron entry into the circulation skin vitamine D3 increases of intestinal absorption of calcium, magnesium, and phosphate, boosts the immune system white adipose tissue leptin reduces energy intake in long term Szinte minden szövetben termelődik hormon.thymus thymosins immunomodulators The hormones Types of the cell‐cell communication Hormones: • possess biological activity • are produced by cells • act by humoral way • are effective in small concentrations • have slow and long term effects • bind to specific, high affinity receptors • 1 type of hormone→ more target tissue electric activity • 1 type of tissue responds to several types of hormones • are released rhythmically Classification of the hormones chemical structure example solubility receptor mechanism of action protein, growth hormone (190 AA) Soluble in water Second messengers Extracellular (on polypeptide, calcitonin (32 AA) (hydrophilic) changes in enzymatic the surface of the activities oligopeptide, oxytocin (9 AA), cell) gene expressional amino‐acid derivates adrenaline, noradrenaline changes steroids estrogens, testosterone gluco‐ Soluble in and mineralocorticoids lipids intracellular Direct effects on gene (hydrophobic) (nuclear, expression cytoplasmatic) amino‐acid derivates thyroxine, triiodothyronine • Hormones in the blood are in free (proteins) or conjugated form ( mostly to albumins i.e. steroids, small molecules) • Free hormones have biological activities only Regulation of the hormone production/release A. Hypothalamus‐pituitary complex (HPC) B. Qualitative or quantitative changes in the blood C. Neuronal regulation Independent from the HPC: • Pineal gland • Parathyroid gland • Islets of Langerhans • Adrenal medulla • Placenta The hypothalamic‐pituitary (hypophyseal) complex – a neuroendocrine system neuroendocrine system: the nervous sytem (hypothalamus) and the endocrine system that cooperate Hierarchic structure The pituitary is connected with the hypothalamus via the infundibulum The brain (encephalon) : The diencephalon: • Forebrain (prosencephalon) • thalamus • telencephalon • hypothalamus • diencephalon • subthalamus • Middle brain (mesecephalon) • epithalamus • Hind brain (rhombenchephalon) Pituitary tumors may cause visual disturbances The hypothalamus sagittal • Biological clock • Salt and fluid homeostasis • Thermoregulation • Autonomic and endocrine center • Energy balance regulation • Integrative function Adeno‐ and neurohypophysis are the main parts of the pituitary Neurohypophysis: Adenohypophysis: Infundibular stalk stem • The adenohypophysis is a glandular, the neurohypophysis is a neuronal tissue. • Neurohypohysis = posterior pituitary: does not produces hormones • Adenohypophysis = anterior pituitary: produces its own hormones • Hypophyseal cleft: between the pars intermedia and pars distalis The adeno‐ and neurohypophysis are both ectodermal, but have different embryological origin telencephalon? Rathke’s stalk Rathke's pouch is a depression in the roof of the developing mouth • Neurohypophysis: neuroectodermal (stomodeum) • Adenohypophysis: ectodermal The hypothalamus contains neurosecretory cells Projectory neurons Parvocellular part Magnocellular part Only storage, but not hormone production! Neurosecretory cell: releases and produces hormones in response to a neuronal stimulus The magnocellular neurons in the hypothalamus project to the neurohypophysis hypothalamic‐neurohypophyseal neurosecretory system Paraventricular nucleus neurohypophysis adenohypophysis Optic tract Median eminence ADH immunohistochemistry, rat hypothalamus coronal section • Fibers of the magnocellular neurons compose the hypothalamic‐hypophyseal tract. • Magnocellular neurons express vasopressin (ADH) or oxytocin (different cells). • Oxytocin stimulates uterus contraction, milk ejection, social bonding. • ADH increases water absorption in the collecting ducts of the kidney nephron. • central diabetes insipidus (polyuria, polydipsia) Oxytocin and vasopressin are transported via the axons connected to carrier molecules called neurophysins Herring bodies: • large clusters of neurosecretory granules at the terminal portion of the axons • oxytocin+neurophysin1 or ADH+neurophysin2 is stored in different terminals • they can be seen at light microscopic level Histology of the pars nervosa pars nervosa 3. 2. 1. pars intermedia 1. unmyelinited axons 2. special glial cells ‐ pituicytes, oval nucleus 3. fenestrated capillaries The hypothalamus contains neurosecretory cells Projectory neurons Parvocellular part Magnocellular part Only storage, but not hormone production! Parvocellular neurons project to the median eminence an release hormones into the portal system Parvocellular cells tuberoinfundibular tract superior hypophyseal artery PRIMARY CAPILLARY BED: median eminence, infundibular stalk portal vessels vein portal vessels SECONDARY CAPILLARY BED: Neurohypophysis Adenohypophysis vein inferior vein hypophyseal artery Hormone rich blood Parvocellular neurons of the hypothalamus regulate hormone production of the adenohypophysis: the tuberoinfundibular neurosecretory system parvocellular nuclei IH RH Feedback (short loop) Feedback (long loop) (Ultrashort feedback loop) Feedback (short loop) Releasing and inhibiting hormones and their targets in the anterior pituitary Diurnal and also episodic (pulsatile) secretion + ++‐ + ‐ + thyroid testes, ovaries liver Periphery mammary adrenal fat, cartilage gland cortex GnRH: gonadotropin releasing hormone or luteinizing‐hormone‐releasing hormone (LHRH) GHRH: growth hormone releasing hormone SS: somatostatin TRH: thyrotropin‐releasing hormone DA: dopamine CRH: corticotropin‐releasing hormone or factor (CRF) Pituitary cell types in the adenohypohysis •Somatotrophes produce growth hormone Acidophils •Lactotrophes produce prolactin chromophil •Thyrotrophes produce thyroid stimulating hormone Basophils •Gonadotrophes produce luteinizing hormone or follicle‐stimulating hormone •Corticotrophes produce adrenocorticotrophic hormone These are cells that have minimal or no hormonal content. Many of the chromophobes may be acidophils or basophils that have degranulated and Chromophobes thereby are depleted of hormone. Some chromophobes may also represent stem cells that have not yet differentiated into hormone‐producing cells. Growth hormone (GH) overproduction underproduction Hypothalamus ‐ + ‐ Pituitary Liver Bone ‐ + + + + + During infancy Muscle Adipose tissue, lipolysis During infancy: Gigantism In adulthood: Acromegaly Maurice Tillet, the „French Angel” 1940 Prolactin (PRL ) ‐ v • Regulation by an inhibitory hormone (dopamine) • Stimulatory: breast feeding, stress • Prolactinoma is a common type of tumor in the pituitary gland, and it causes infertility The thyroid gland Hormones: 1. Thyroxine (T4), triiodothyronin (T3) 2. Calcitonin – regulation of the calcium homeostasis The thyroid gland is located in front of the trachea at the level of the larynx in the neck crycoid cartilage pyramidal lobe (present in 50%) right lobe isthmus left lobe • Moves up and downward during swallowing – medical examination Frontal view Low power microscopic view of thyroid tissue by H&E staining thyroid gland septum colloid folliculus adipose tissue vessels parathyroid gland H&E staining MICHAEL ROSS/SCIENCE PHOTO LIBRARY Folliculi compose the structural units of the thyroid capsule colloid parafollicular cell, (C , clear‐cell) septum lobule follicle (0.2‐1.0 mm) principal or follicular cell fenestrated capillary reticular