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Home , Chromophil, Parafollicular cell, Parathyroid chief cell

The

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 ; • 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

Endocrine system

Not all endocrine glands are under hypothalamic control. The endocrine system

Classic endocrine organs

Pituitary gland (hypophysis) Pajzsmirigy, and Thyroid and mellékpajzsmirigy Parathyroid glands Parathyroid glands

Adrenal gland

Pancreas: Islets of Langerhans

Endocrine gland: • Epithelial origin (except the ) • No excretory ducts, unlike in the exocrine glands (i. e. salivary gland) • Lobes, and lobules, separated by connective tissue septa • 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

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, (32 AA) (hydrophilic) changes in enzymatic the surface of the activities oligopeptide, oxytocin (9 AA), cell) gene expressional amino‐acid derivates , 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 • • Islets of Langerhans • Adrenal medulla • 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 = : does not produces hormones • Adenohypophysis = : produces its own hormones • Hypophyseal cleft: between the 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 ‐ , 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 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: TRH: thyrotropin‐releasing hormone DA: 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

‐ + + +

+ + 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 • is a common type of tumor in the , 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

, (C , clear‐cell) septum

lobule

follicle (0.2‐1.0 mm)

principal or follicular cell fenestrated capillary reticular connective tissue (lymphatic vessels, nerves) Principal (follicular) and C‐cells produce different hormones

Follicular cell (F) : F • simple squamous or cuboidal epithelium • basofil cytoplasm • produces thyroglobulin =colloid • add or substract thyroglobulin into and from Colloid the cavity of the folliculus: ‐glycoprotein (~120 tyosine) ‐precursor of thyroid hormones

Parafollicular cell (C): • light or clear cytoplasm • localizes in the epithelium inside the basal lamina or in groups between the folliculi • produces calcitonin H&E staining Thyroglobulin production and hormone release happens paralelly Blood Follicular cavity Follicular cell

thyroid peroxidase +

MIT: monoiodotyrosine T4= DIT+DIT DIT: diiodotyrosine T3= MIT+DIT Functional phases of the follicle

Hypoactive phase: flatter epithelium, Active phase: columnar epithelium, big cavity – storage of colloid schrinked cavity – little colloid, reuptake

Hormone production is stimulated by, darkness and cold temperature and it is elevated during pregnancy. Production of T3 and T4 is regulated by the hypothalamic‐ pituitary thyroid axis

TSH: •Stimulates T3 and T4 production •Stimulates proliferation of the follicular cells negative feedback T3 : Pituitary •Necessary for the normal development of (‐) the central nervous system

effect • Regulates production of the extracellular matrix components (skin) •Metabolic effects: increases basal metabolic rate Thyroid increases heat production •Increases the heart rate •Regulates the cholesterol homeostasis •Influences the glucose homeostasis Hypothalamo‐pituitary‐thyroid (HPT ) axis Over‐ and underfunctioning of the thyroid gland

hypothyreosis = mixodema cretinism untreated treated congenital hypothyreoidism

Hypo‐ and hypertyroidism both cause goiter

Dietary iodine is important for the normal function!

Basedow disease hyperthyreosis Parathyroid glands are small, oval‐shaped glands near the posterior aspect of the thyroid gland

Superior glands‐

Inferior glands‐

dorsal view

• Each gland has its own fibrous capsule Two main cell types are the principal and oxyphil cells

trabeculae

OX OX

Principal or chief cells: ● small, polygonal, central round nuclei, contain secretory granules of (PTH) and may contain glycogen Oxyphil cells: ● larger than chief cell, oval, acidophilic cytoplasm ● no secretory granules, no hormone production Calcitonin and parathyroid hormone regulate the Ca2+ homeostasis calcitonin parathyroid hormone (PTH) production thyroid C‐cell blood Ca2+ level reduces increases regulation blood Ca2+ level blood Ca2+ level bone break down reduces increases Ca2+ reabsorption in the reduces increases kidney Ca2+ absorbtion in the gut reduces increases (indirectly) active vitamine‐D ‐increases production blood phosphate level ‐ reduces (renal reabsorption)

Lack of PTH‐tetany, lack of calcitonin‐no symptomps. The

It is located on the upper pole of the kidney.

medulla cortex

• 10% • 90% • brownish‐red • yellowish • catecholamines: • corticosteroids adrenaline, noradrenaline • mesodermal • ectodermal‐ capsule • thick, dense connective tissue The cortex is subdivided into three concentric layers

1. 1. Thin outer layer, small cells arranged in rounded clusters or curved columns.

2. Thick middle layer, large cells 2. arranged in two cell thick cords.

3. Thin inner layer, the cells are arranged in a net‐like structure. 3.

Azan staining cells secrete mineralocorticoids, mainly aldosterone

arterial plexus (*) capsule This zone regulates the fluid and osmotic balance *

septum Glomerulosa cells: • columnar or pyramidal • ovoid groups (glomeruli) • fenestrated capillaries

glomerulus Aldosterone: capillaries • increases Na+, decreases K + resorption in the distal tubules in zona kidney glomerulosa • regulated by angiotensin II, blood K+, Na+concentration, (ACTH) Zona fasciculata cells secrete glucocorticoids

Glucocorticoid: glucose+cortex+steroid • Mainly cortisol in humans Fasciculata cells: • 2 cell‐thick cell cords, separated by sinusoids • numerous lipid droplets in the cytoplasm‐”foamy” appearence

Effects of cortisol: • protects against stress (“stress” hormone) • increases blood glucose level, • promotes metabolism of lipids, carbohydates and proteins • supresses inflammation and the immune system • inhibits bone formation‐ promotes sinuses • iInfluences memory, and learning (septa) • it is regulated by ACTH The hypothalamic – pituitary – adrenal (HPA) axis regulates the secretory activity of the zona fasciculata and reticularis

capsule

z. glomerulosa aldosterone

cortisol z. fasciculata

z. reticularisandrogens z. reticularis

Systematic steroid treatment cannot be stopped suddenly, it can cause schock! The stress concept

Hans Selye

infectious diseases

cancer asthma

heart diseases STRESSZ depression (1907 - 1982)

Stress (1960): ulcer skin conditions • „non‐specific reaction of the body to stimuli post traumatic stress disease (stressors) that disturb the steady‐state condition of the homeostasis and require adaptation • Eustress (positive) and distress (negative) • acute and chronic stress A Selye féleThe general adaptation syndrome (GAS) Általános Adaptációs Szindróma fázisai

• Chronic diseases develop in the resistance stage • Some stress (cortisol) is needed to the optimal performance

Yerkes-Dodson’s law cells secrete gonadocorticoids (androgens)

The androgens are transformed into testosterone or estrogen

Reticularis cells: • irregular network of small cells • ACTH regulated hormone production

Androgens: • are less significant in adults • are important during embryonic development‐ the function is not known exactly • in women contribute to the estrogen production after menopause • regulate function of the sebaceous glands Medullary cells secrete adrenaline and noradrenaline

Cortex

Medullary cells: • relatively large, round or columnar, basophilic • neurosecretory cells, modified neurons • sympathetic innervation • secretory granules: adrenaline and noradrenaline production in different cell types • chromaffin reaction: the hormones are oxidized by chromate salts resulting brownish color

• adrenaline: stress reaction: Fight or flight • noradrenaline: vasoconstriction at the periphery

Chromate salt treatment Sympathetic activation: Fight or flight (Cannon’s) reaction

vasoconstriction

adrenal • energy mobilization • preparation for escape, or fight • generalized

vasoconstriction Pathologies

Cushing disease: high cortisol level

Addison disease: low cortisol level The : the testis

Seminiferous tubule

https://mmegias.webs.uvigo.es/02‐english/2‐organos‐a/guiada_o_a_07re‐masculino.php

• Located within the scrotum, surrounded by a connective tissue capsule • Descends from the abdominal cavity during the embryonic development • Lobules‐connective tissue septa • Exocrine (sperm production) and endocrine (testosterone production) organ • Convoluted seminiferous tubules: Sertoli‐cells (“nurse” cells) and developing sperm cells • Continously functions starting from puberty • Spermatogenesis: 64 days • Leydig cells: in the interstitium, testosterone production • Regulated by the HPG axis The hypothalamic‐pituitary –gonadal (HPG) axis

FSH: acts on the Sertoli cells, increases spermatogenesis

+ LH: acts on the Leydig cells, increases hormone production

Testosterone: promotes development + of male reproductive tissues and + secondary sexual characteristics

Negative feedback: • inhibin by Sertoli cells • testosterone by Leydig cells

Factors that affect the spermatogenesis:

• temperature • stress • inflammation (mumps) • ishemia • radioactivity • chemotherapy The gonads: the

• In the pelvis, bilaterally • Connective tissue capsule Parts: • Cortex: developing follicles • Medulla: vessels, nerves Follicular development

• Oocytes are present at birth • Cyclic function from the puberty till the menopause • Regulated by the HPG axis

• follicle: oocyte + follicular cells • different developmental stages of the follicles are present simultaneously, • follicular cells proliferate, liquor accumulates inside the follicle • follicular cells: estrogen, inhibin production • Graafian follicule: ovulation • after ovulation: –progesterone release • corpus luteum degeneration‐menstruation • pregnancy: the corpus luteum persists for 2 month and produces progesterone The menstrual cycle: ovarian and uterine cycles FSH/LH: • promote follicular maturation and hormone secretion of the follicular cells LH: • LH surge at ovulation • mainanance of the corpus luteum Estrogens: • secondary sexual characteristics • positive feedback on LH before ovulation • uterine mucosa (endometrium) proliferation • maintenance of bone density • cardiovascular protection • memory enchancement • menopause!

Progesterone: • endometrium secretory phase • inhibition of uterine contractions • immune system modification • elevation of the body temperature (ovulation) • inhibition of lactation during pregnancy

Inhibin: FSH/LH negative feedback The placenta

• Fetal and maternal parts (chorion and uterine mucosa) • Human chorionic gonadotropin (hCG) hormone: promotes the maintenance of the corpus luteum at the beginning of the pregnancy • Pregnancy test: detection of HCG at early stage of the pregnancy • After regression of the corpus luteum the placenta produces: estrogens and progesterone: prevent abortion, promote proliferation of the uterine tissue and prepare it for the delivery, prepare the breasts for lactation The pancreas

exocrine

endocrine

Exocrine secretum: digestive enzymes ‐ leave the pancreas through the ductal system, and get into the duodenum. Endocrine secretum: hormones ‐ leave the pancreas through the capillaries and get into the circulation. The islets of Langerhans are highly vascularised by fenestrated capillaries

H&E: light staining The islets of Langerhans ‐regulation of the blood glucose level

A cells – glucagon – increases the amount of glucose in blood B cells – insulin – decreases the amount of glucose in blood D cells ‐somatostatin – inhibits the other two F cells – pancreatic polypeptide – stimulates stomach chief cells, inhibits bile and bicarbonate secretion Epiphysis or pineal gland

Develops from the diencephalon, 5‐8 mm big The pineal complex: the pineal gland and the parietal eye

• Parietal eye (organ): photoreceptive in reptiles, humans do not have it. • An anterior evagination of the epiphysis. • Only few of today’s lizards have it. • Thermoregulation, reproduction, orientation. • Parietal nerve:. does not project to the visual cortex. The pineal gland produces melatonin

1917. Feeding extract of the pineal glands of cows lightened tadpole skin.

1958: isolation of the hormone from bovine pineal gland extracts.

„mela” (melanin) + „tonin „ ()

mid‐1960s: the pineal gland is recognized as a component of the endocrine system:

• melatonin is produced in darkness (night) • adjusts our biological clock to the actual night‐ dark cycle‐regulates the sleep‐wake cycle • influences the seasonal reproduction in photosensitive species, • sympathetic innervation of the gland is needed to be functional Histology of the pineal gland

• ‐melatonin production • Glial cells • Mast cells • Connective tissue, septa • Nerve fibers • Capillaries • Brain sand The pineal gland is a mineralizing tissue

• Brain sand: Fluorides enhance calcium accumulation Thank you for your attention!

Keukenhof Gardens, Hollandia