Endocrine system 1 General data on endocrine glands

Endocrine system 1. General data on endocrine glands 2. Morphofunctional characteristics of the endocrine glands a) Pituitary gland b) Epiphysis c) Thyroid gland d) Parathyroid glands e) Thymus f) Adrenal glands g) Pancreas h) gonads 3. Organogenesis of the endocrine system Lecturer: Ph. D, professor Tamara Hacina

Characteristics of the endocrine system • The endocrine system functions in the regulation of body activities. • It acts through chemical messengers called hormones that influence growth, development, metabolic activities. • Its action is measured in minutes, hours, or weeks & is more generalized than the action of the nervous system.

The endocrine system • The endocrine system comprises a group of ductless glands that secrete chemical messenger substances, called hormones, into the bloodstream. • Hormones are responsible for the long-term regulation of many bodily functions. • The endocrine system includes the pituitary, thyroid, parathyroid, thymus and adrenal glands, and the pancreas and gonads (ovaries and testes).

Common features of the endocrine glands • Superior blood-supply: fenestrated capillaries, on at least one side • Ductless glands • Cells organized in “chunks”: blocks, islands, plates, cords • Epithelial in origin (an or two exceptions) • Polihedral cells with round nucleus • Plentifull organelle content (indicates synthesis)

• The endocrine system acts with nervous system to coordinate the body's activities. • Both systems enable cells to communicate with others by using chemical messengers. • The endocrine system uses chemical messengers called hormones that are transported by the circulatory system (blood). They act on target cells that may be anywhere in the body. • The endocrine system is slower than the nervous system because hormones must travel through the circulatory system to reach their target. • Target cells have receptors that are specific to the signaling molecules. The binding of hormones to the receptors on or within the target cell produces a response by the target cell.

Hormones Hormones are: Ø chemical messengers Ø mostly proteins, amines (small molecules derived from amino acids) or steroids Ø secreted by endocrine glands (glands without ducts) Ø carried in bloodstream to target organs Ø change the way in which cells function Ø target specific Groups of hormones : 1. Amono acid derivatives: epinephrine, norepinephrine, thyroxine 2. Small peptides: encephalin, vasopressin, TRH 3. Proteins: nerve growth factor, insulin, parathormone, TSH, EGF 4. Steroids: cortisol, progesterone, testosterone, estradial.

Chemical Classificaton of Hormones • Steroid Hormones: – Lipid soluble – Diffuse through cell membranes – Endocrine organs • • Adrenal cortex Ovaries Testes Placenta Receptors for steroid hormones are found in the cell’s cytoplasm or in its nucleus • Nonsteroid Hormones: – Not lipid soluble – Received by receptors external to the cell membrane – Endocrine organs • • • Thyroid gland Parathyroid gland Adrenal medulla Pituitary gland pancreas Receptors for nonsteroid hormones are located on the cell membrane

Mechanisms of (a) Humoral: in response to changing levels of ions or nutrients in the blood hormone (b) Neural: stimulation by nerves (c) Hormonal: stimulation received from other hormones release 10

Hypothalamus Pituitary gland (hypophysis) Pineal body The endocrine and nervous systems are so closely associated that they are collectively called the neuroendocrine system. The main control center is the hypothalamus, also known as the “master switchboard”. Suspended from the hypothalamus by a stalk is the pituitary gland. The hypothalamus sends messages to the pituitary gland, in turn, releases hormones that regulate body functions.

The Pineal Gland

Pineal Gland The pineal gland was called the "third eye" by ancient people. It was thought to have mystical powers. The pineal does contain a complete map of the visual field of the eyes, and it plays several significant roles in human functioning. It is the center for the production of the hormone melatonin. It regulates daily body rhythms, most notably the day/night cycle, prevents jet lag, is implicated in seasonal affective disorder, coordinates fertility, and allows for deep restful sleep patterns. The pineal gland or in its Latin and anatomical name "epiphysis cerebri", is a tiny bean-size brain organ or "gland" which is connected to the brain and nervous systems through a complex network of bidirectional links. The "pineal master gland" acts as a true "director of the hormonal orchestra" in the course of growth, puberty, fertility and aging.

• At the end of a short stalk on the roof of the diencephalon • Pinealocytes with dense calcium particles • Can be seen on x-ray (because of Ca++) • Melatonin helps regulate the cardium rhythm – The biological clock of the diurnal (night/day) rhythm – Complicated feedback via retina’s visual input The Pineal Gland

Why is the Hypothalamus so Important? • Secretes regulatory homones – RH – RIH • "Directs" pituitary

Hypothalamus (general) • Connection to pituitary: – Neuronal to POSTERIOR PITUITARY – Endocrine to ANTERIOR PITUITARY • RH = Pituitary releasing hormones • RIH = Pituitary release inhibiting hormones

Neurosecretory Cells 1. Specialized neurons – Synthesize and secrete hormones 2. Extend from HYPOTHALAMUS to POSTERIOR PITUITARY

Neurosecretory cells in Hypothalamus • Nuclei synthesize and secrete hormones • Neuronal connection to POSTERIOR pituitary • Antidiuretic Hormone (ADH), Oxytocin

Posterior Pituitary Hormones • Manufactured in Hypothalamus, released from Post. Pit. • Oxytocin – Target = smooth ms. Uterus and Breast (&brain) – Function = labor and delivery, milk ejection, (pair bonding) • ADH (Vasopressin AVP) – Target = kidneys – Function = water reabsorption

Pituitary Gland The pituitary gland, which is located in the center of the skull, just behind the bridge of the nose, is about the size of a pea. It is an important link between the nervous system and the endocrine system and releases many hormones which affect growth, sexual development, metabolism and the system of reproduction. The "hypothalamus" is a tiny cluster of brain cells just above the pituitary gland, which transmits messages from the body to the brain. The pituitary gland has two distinct parts, the anterior and the posterior lobes, each of which releases different hormones which affect bone growth and regulate activity in other glands. This gland was once believed to be the main controlling gland of the body, but we now know that, it is subservient to a master gland called the hypothalamus, which is the needed link between the pituitary gland the brain. This "master gland" is really a way station between the body and the brain and sorts out messages going to and from the brain. It responds to the body through the pituitary gland, which is suspended just below it. It sometimes replies by nerve impulses and sometimes with needed hormones. The pituitary gland then makes hormones of its own in answer to the body's needs.

MASTER GLAND • Anterior and posterior portions • Posterior connected to hypothalamus by infundibulum • Anterior connected via blood stream Pituitary gland

The pituitary gland is: • a pea-sized structure located at the base of the brain. • an extension of the hypothalamus. • consists of an anterior lobe and a posterior lobe. • produces hormones that control other glands and many body functions.

Releasing hormones (factors) of hypothalamus Secreted like neurotransmitters from neuronal axons into capillaries and veins to anterior pituitary (adenohypophysis) TRH (thyroid releasing hormone) turns on TSH CRH (corticotropin releasing hormone) - turns on ACTH Gn. RH (gonadotropin releasing hormone) - turns on FSH and LH PRF (prolactin releasing hormone) turns on PR Inhibiting hormones of hypothalmus PIF (prolactin inhibiting factor) -----turns off PRL GH (growth hormone) inhibiting hormone ---turns off GH GHRH (growth hormone releasing hormone) - turns on GH The hypothalamus controls secretion of hormones which in their turn control the secretion of hormones by the thyroid gland, the adrenal cortex and gonads: in this way the brain controls these endocrine glands

Hypothalamus____ Pituitary______ (hypophysis)

From the posterior pituitary (neurohypophysis) • ADH (antidiuretic hormone or vasopressin) stimulates the kidneys to reclaim more water from the urine, raises blood pressure. • Oxytocin prompts contraction of smooth muscle in reproductive tracts, in females initiating labor and ejection of milk from breasts.

The Pituitary Sits in hypophyseal fossa: depression in sella turcica of sphenoid bone Pituitary secretes 9 hormones Two divisions: • Anterior pituitary (adenohypophysis) 1. TSH 2. ACTH 3. FSH 4. LH ____ 5. GH 6. PRL 7. MSH The first four are “tropic” hormones, they regulate the function of other hormones _________________________________ • Posterior pituitary (neurohypophysis) 8. ADH (antidiuretic hormone), or vasopressin 9. Oxytocin

The pituitary gland Thyroid stimulating hormone Adrenocorticotropic hormone Gonadotropic hormones (FSH & LH) Growth hormone Prolactin ANTERIOR LOBE POSTERIOR LOBE Antidiuretic hormone Oxytocin

Anterior pituitary gland Gland Anterior pituitary Principle hormones Thyroid stimulating hormone (TSH) Action Regulates thyroid gland Adrenocortico tropic hormone Regulates adrenal cortex (ACTH) Gonadotropic hormones Follicle stimulating hormone (FSH) Luteinising hormone (LH) Regulates gonads Growth hormone (GH) Regulates growth in children Prolactin Regulates milk production

Posterior pituitary gland Gland Posterior pituitary gland Principle hormones Action Antidiuretic hormone Regulates water reabsorption from (ADH) kidneys Oxytocin Allows milk letdown/suckling reflex Initiates labor Maternal behaviour

Hypersecretion of pituitary gland

Hyposecretion of the pituitary gland

Simmonds disease, also known as anterior pituitary hypofunction, is lack secretion of pituitary hormones, lesions of pituitary or hypothalamus involve the endocrine function in pituitary gland. when the pituitary had destroyed, may produce the performance of endocrine gland hypofunction, the mainly involvement of the gland is sex gland, thyroid and adrenal cortex.

The thyroid gland is shaped like a butterfly and usually weighs less than one ounce. The thyroid cartilage covers the larynx and produces the prominence on the neck known as the "Adam's Apple". The thyroid gland controls the rate at which the body produces energy from nutrients. If the body does not get enough iodine, the thyroid gland cannot produce a proper amount of hormones for this conversion process. The result can be a goiter, an enlargement of the thyroid gland. In some parts of the world, iodine is so scarce that most of the population have goiters. Thyroid Gland

• Thyroid is composed of spherical follicles – Follicle cells: produce thyroglobulin, the precursor of thryoid hormone (thyroxin) – Colloid lumen is of thyroglobulin – Parafollicular “C” cells: produce calcitonin 37

Action of thyroid hormons

Hypersecretion of the thyroid glands at adults

Exophthalmos of Grave’s disease Enlarged thyroid (goiter) from iodine deficiency

Malfunctions of Thyroid gland 1. Cretinism (in infancy) – dwarfs, retarded hypothyroidism 2. Myxedema (in adults) – swelling, slowness - hypothyroidism 3. Regular Goiter – too little iodine yields pituitary response 4. Toxic Goiter – TSH overproduction

Hyposecretion of the thyroid gland at adults

Hyposecretion of the thyroid gland in childhood

Hyposecretion of the thyroid gland

Parathyroid Glands • There are four parathyroid glands, which are located behind the thyroid. • The sole purpose of the gland is to regulate the calcium level in our bodies within a very narrow range in which our muscular and nervous systems can function properly.

Functions of thyroid & parathyroid hormons

Thyroid & parathyroid glands Gland Thyroid Parathyroid Principle hormones Action Thyroxine Stimulates metabolism/releases glucose Calcitonin Lowers blood calcium Parathyroid hormone Raises calcium levels

Cronical hypoparathyroidism

Adrenal Gland

Adrenal (suprarenal) glands (“suprarenal” means on top of the kidney) • Each is really two endocrine glands – Adrenal cortex (outer) – Adrenal medulla (inner) • Unrelated chemicals but all help with extreme situations 53

Adrenal gland Gland Adrenal cortex Adrenal medulla Principle hormones Action Mineralocorticoids e. g. Sodium metabolism aldosterone Glucocorticoids e. g. cortisol Stress response/glucose metabolism Gonadocorticoids e. g. testosterone Secondary sexual characteristics Adrenaline (epinephrine) Fight or flight response Noradrenaline (norepinephrine)

Microscopic structure of adrenal gland

Adrenal Gland Adrenal cortex Secretes lipid-based steroid hormones, called “corticosteroids” MINERALOCORTICOIDS Aldosterone is the main one GLUCOCORTICOIDS Cortisol (hydrocortisone) is the main one Adrenal medulla Secretes epinephrine and norepinephrine

Aldosterone, the main mineralocorticoid • Secreted by adrenal cortex in response to a decline in either blood volume or blood pressure (e. g. severe hemorrhage) – Is terminal hormone in renin-angiotensin mechanism • Prompts distal and collecting tubules in kidney to reabsorb more sodium – Water passively follows – Blood volume thus increases

Cortisol, the most important glucocorticoid • It is essential for life • Helps the body deal with stressful situations within minutes – Physical: trauma, surgery, exercise – Psychological: anxiety, depression, crowding – Physiological: fasting, hypoglycemia, fever, infection • Regulates or supports a variety of important cardiovascular, metabolic, immunologic, and homeostatic functions including water balance People with adrenal insufficiency: these stresses can cause hypotension, shock and death: must give glucocorticoids, eg for surgery or if have infection, etc.

Adrenal medulla • Part of autonomic nervous system • Spherical chromaffin cells are modified postganglionic sympathetic neurons – Secrete epinephrine and norepinephrine – Amine hormones – Fight, flight, fright • Vesicles store the hormones

Pathology of Adrenal gland Cushing’s syndrome: Usually caused by an ACTH-secreting pituitary tumor, rarely by tumor of adrenal cortex, iatrogenic

disease Hyposecretion (under secretion) of adrenal cortex Usually involves cortisol and aldosterone: low blood glucose and sodium, severe dehydration, fatigue, loss of appetite, abdominal pain

Note the generalised skin pigmentation but ispecially the deposition in the palmer skin, nails & gums.

The pancreas Ilets of Langerhans Pancreas • Endocrine tissue in the pancreas (the islets of Langerhans) secrete hormones that regulate the blood sugar level.

Pancreas • The Pancreas has two main functions: • to produce pancreatic endocrine hormones, which help regulate Located slightly behind the stomach many aspects of our metabolism, • Insulin: reduces blood glucose and – Facilitates glucose transport into the cells • to produce – Promotes glycogenesis pancreatic – Inhibits gluconeogenesis digestive enzymes. • Glucagon: increases blood glucose

• Glucose must not only be delivered to the cells, it must also be taken up by them. That job relies on insulin. • Exercise may enhance insulin’s binding to receptors on the muscle fiber. • Up-regulation (receptors) occurs with insulin after 4 weeks of exercise to increase its sensitivity (diabetic importance). • When low plasma glucose levels occur, the catecholamines are released to accelerate lypolysis. • Triglycerides are reduced to free fatty acids by lipase which is activated by: – – Cortisol Epinephrine Norepinephrine Growth Hormone

The Pancreas Exocrine and endocrine cells • Acinar cells (forming most of the pancreas) – Exocrine function – Secrete digestive enzymes • Islet cells (of Langerhans) – Endocrine function 73

Thymus The thymus is a gland that forms part of the immune system. It is situated in the upper part of the chest, behind the breastbone, and is made up of two lobes that join in front of the trachea. Each lobe is made of lymphoid tissue, consisting of tightly packed white blood cells and fat. The thymus enlarges from about the 12 th week of gestation until puberty, when it begins to shrink. Its function is to transform lymphocytes (white blood cells developed in the bone marrow) into T-cells (cells developed in the thymus). These cells are then transported to various lymph glands, where they play an important part in fighting infections and disease. Swelling of lymph glands and fever are a signal that immune cells are multiplying to fight off invaders of the body: bacteria, fungi, viruses or parasites.

Male testes Gland Gonads Principle hormones Female ovaries Action Male gonads The testes Testosterone Male secondary sexual characteristics Female gonads The ovaries Oestrogen (estrogen) • Female secondary sexual characteristics • Development of the endometrium • Maintenance of endometrium Progesterone

The scrotum is a sac that hangs under the penis and holds the testes. It is divided internally into two halves by a membrane; each half containing a testis. It has an outer layer of thin, wrinkled skin over a layer of tissue which contains muscle. The testicle lies inside the scrotum and produces as many as 12 trillion sperm in a male's lifetime, about 400 million of which are ejaculated in one average intercourse. Each sperm takes about seventy-two days to mature and its maturity is overseen by a complex interaction of hormones. The scrotum has a built-in thermostat, which keeps the sperm at the correct temperature. Testes It may be surprising that the testicles should lie in such a vulnerable place, outside the body, but it is too hot inside. The sperm production needs a temperature which is three to five degrees below body temperature. If it becomes too cool on the outside, the scrotum will contract to bring the testes closer the body for warmth.

Ovaries The ovaries produce a female hormone, called estrogen, and store female sex cells, or “ova. ”

The Gonads (testes and ovaries) main source of the steroid sex hormones • Testes – – Interstitial cells secrete androgens Primary androgen is testosterone • Maintains secondary sex characteristics • Helps promote sperm formation • Ovaries – – – Androgens secreted by thecal folliculi • Directly converted to estrogens by follicular granulosa cells Granulosa cells also produce progesterone Corpus luteum also secretes estrogen and progesterone

Functions of the gonads

Regulation of the ovarian and menstrual cycles • The ovarian cycle (the monthly sequence of changes that take place in the ovaries) is regulated by the pituitary hormones follicle stimulating hormone (FSH) and luteinising hormone (LH). • The menstrual cycle (the monthly sequence of changes that take place in the uterus) is regulated by the ovarian hormones estrogen and progesterone. • Both cycles are regulated by complex feedback processes.

Hormonal action on the female reproductive organs Progesterone Luteinising hormone (LH) Estrogen Follicle stimulating hormone (FSH) Ovarian hormone (corpus luteum) Anterior pituitary hormone Ovarian hormone (ovarian follicle) Anterior pituitary hormone Target – endometrium Target – corpus luteum Target – endometrium Target – ovarian follicle Role – maintenance of endometrium Roles – ovulation, Role – repair of maintenance endometrium after of corpus menstruation luteum Predominant in first part of cycle second part of cycle Predominant in second part of cycle Role – maturation of ovarian follicle Predominant in first part of cycle

Hormonal control of ovarian/menstrual cycle

Endocrine cells in various organs continued • The heart: atrial natriuretic peptide (ANP) – Stimulates kidney to secrete more salt – Thereby decreases excess blood volume, high BP and high blood sodium concentration • GI tract & derivatives: Diffuse neuroendocrine system (DNES) • The placenta secretes steroid and protein hormones – Estrogens, progesterone – CRH – HCG • The kidneys – Juxtaglomerular cells secrete renin • Renin indirectly signals adrenal cortex to secrete aldosterone – Erythropoietin: signals bone marrow to increase RBC production • The skin – Modified cholesterol with uv exposure becomes Vitamin D precursor – Vitamin D necessary for calcium metabolism: signals intestine to absorb 85 CA++

Pathology • Pituitary – – Gigantism –too much GH in childhood Acromegaly – too much GH in adulthood Pituitary dwarfs – too little GH in childhood Diabetes insipidus - too much ADH • Pancreas – Diabetes mellitus – one type of insulin (not enough) • Thyroid – Hyperthyroidism, commonest is Grave’s disease (autoimmune) – Hypothyroidism • In childhood leads to cretinism • Endemic goiter from insufficient iodine in diet • Adult hypothyroidism (myxedema): autoimmune

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