Lecture # 14: The Endocrine System 1

1. The Endocrine System (Chapter 17) Lecture # 14: The Endocrine System 1 Objectives 1- To define hormone and Endocrine System. 2- To describe the gross and microscopic anatomy of the different organs of the endocrine system. 3- To contrast endocrine and exocrine glands. 4- To compare and contrast the nervous and the endocrine systems. 5- To explain how the pituitary gland is controlled by the hypothalamus and its target organs. 6- To list the hormones produced by the principal glands of the endocrine system, and to describe the functions of these hormones.

2. Overview of the Endocrine System • Internal communication is necessary for coordination of cell activities. There are four principal mechanisms of communication between cells: • 1- Gap junctions • They are pores in cell membrane that allow signaling molecules, nutrients, and electrolytes to move from cell to cell. • 2- Neurotransmitters They are released from neurons to travel across synaptic cleft to second cell. • 3- Paracrine (local) hormones • They are secreted into tissue fluids to affect nearby cells. • 4- Hormones • They are chemical messengers that travel in the bloodstream to other tissues and organs.

3. Differences Between the Nervous and the Endocrine Systems Communications • Nervous: Both electrical and chemical. • Endocrine: Only chemical. Speed and persistence of response • Nervous: It reacts quickly (1 - 10 msec), stops quickly. • Endocrine: It reacts slowly (hormone release in seconds or days), effect may continue for weeks. Adaptation to long-term stimuli • Nervous: The response declines (adapts quickly). • Endocrine: The response persists (adapts slowly). Area of effect • Nervous: The effect is targeted and specific (one organ). • Endocrine: The effect is more general, widespread effects (many target organs).

4. Similarities Between the Nervous and the Endocrine Systems Several chemicals function as both hormones and neurotrans-mitters: • Norepinephrine, cholecystokinin, thyrotropin-releasing hormone, dopamine and antidiuretic hormone. Some hormones secreted by neuroendocrine cells (neurons) release their secretion into the bloodstream: • Oxytocin and catecholamines. Both systems may have overlapping effects on same target cells: • Norepinephrine and glucagon cause glycogen hydrolysis in liver. Both systems continually regulate each other: • Neurons trigger hormone secretion and hormones stimulate or inhibit neurons. Target organs or cells: Only those organs or cells that have receptors for a neurotransmitter or a hormone can respond to it.

5. Hormones: • They are chemical messengers that are transported by the blood-stream and stimulate physiological responses in cells of another tissue or organ, often a considerable distance away. Endocrine Glands: • They are organs that are traditional sources of hormones. Characteristics of Endocrine Glands: Characteristics of Exocrine Glands: • They contain dense, fenestrated capillary networks which allows easy uptake of hormones into bloodstream. They have ducts that carry secretions to an epithelial surface or the mucosa of the digestive tract. They produce “external secretions”. • They have no ducts. • Their secretions have an extracellular effects (food digestion). • Their secretions (hormones) are called “internal secretions”. • Hormones have an intracellular effects such as altering target cell metabolism.

6. Major Organs of the Endocrine System Pineal gland Hypothalamus Pituitary gland Thyroid gland Thymus Adrenal glands Pancreas Parathyroid glands Posterior view Gonads: Testis (male) Ovary (female)

8. The Hypothalamus and the Pituitary Gland The hypothalamus and the pituitary gland have the greatest influence in regulating the entire endocrine system. The hypothalamus secrets releasing hormones (RH) that trigger secretions of all of the anterior pituitary gland except prolactin. Thalamus RH The pituitary gland secrets hormones that control other glands. Hypothalamus Optic chiasm Pituitary gland Mammillary body

9. Anatomy of the Hypothalamus and the Pituitary Gland Anterior Posterior Hypothalamus: Third ventricle of brain Paraventricular nucleus Supraoptic nucleus Adenohypophysis: Neurohypophysis: Pars tuberalis Median eminence Stalk (infundibulum) Anterior lobe (pars distalis) Hypothalamo–hypophyseal tract Posterior lobe (pars nervosa)

10. Hypothalamic and Pituitary Hormones Hypothalamic Hormones that trigger the anterior pituitary gland: 1-Gonadotropin releasing hormone (GnRH) Four releasing hormones: 2- Thyrotropin-releasing hormone (TRH) 3- Corticotropin-releasing hormone (CRH) Paraventricular nucleus 4- Growth hormone–releasing hormone (GHRH) Supraoptic nucleus Hypophyseal portal system: 1- Prolactin-inhibiting hormone (PIH) Two inhibiting hormones: 2- Somatostatin Primary capillaries Portal venules The Anterior Pituitary or Adenohypophysis releases: Secondary capillaries 1- Follicle-stimulating hormone (FSH) Gonadotropins 2- Luteinizing hormone (LH) 3- Thyroid-stimulating hormone (TSH) 4- Adrenocorticotropic hormone (ACTH) 5- Growth hormone (GH) 6- Prolactin (PRL)

11. Anterior Pituitary Hormones Gonadotropin-releasing hormone (GnRH) Thyrotropin-releasing hormone (TRH) Corticotropin-releasing hormone (CRH) Growth hormone–releasing hormone (GHRH) Growth hormone (GH) Prolactin (PRL) • It stimulates mitosis and cellular differentiation and thus promotes tissue growth throughout the body. • After birth stimulates the mammary glands to synthesize milk. Also it enhances secretion of testosterone by testes. Liver PRL GH • Induces the liver to produce insulin-like growth factors (IGF-I and IGF-II) that • stimulate target cells in diverse tissues IGF Fat, muscle, bone Thyroid-stimulating hormone (TSH) TSH ACTH Adrenocorticotropic hormone (ACTH) • It stimulates secretion of thyroid hormone. Gonadotropins It stimulates the adrenal cortex to secrete glucocorticoids. FSH LH Follicle-stimulating hormone (FSH) Luteinizing hormone (LH) • It stimulates secretion of ovarian sex hormones, development of ovarian follicles, and sperm production . • It stimulates ovulation, stimulates corpus luteum to secrete progesterone, stimulates testes to secrete testosterone.

12. Oxytocin (OT) • It is released during sexual arousal and orgasm. • It stimulates uterine contractions and propulsion of semen. • It promotes feelings of sexual satisfaction and emotional bonding between partners. Oxytocin (OT) Paraventricular nucleus • It stimulates labor contractions during childbirth. Supraoptic nucleus • It stimulates flow of milk during lactation. Antidiuretic hormone (ADH) • It promotes emotional bonding between lactating mother and infant. Posterior pituitary or Neurohypophysis stores and releases: Antidiuretic hormone (ADH) • It increases water retention thus reducing urine volume and prevents dehydration. Oxytocin (OT) Antidiuretic hormone (ADH) • It is also called vasopressin because it can cause vaso-constriction.

13. Control of Pituitary Secretion 1- Hypothalamic and Cerebral Control -Control of the anterior lobe • The releasing hormones and inhibiting hormones from hypothalamus control the anterior lobe. In cold weather, pituitary stimulated by hypothalamus to release TSH, leads to generation of body heat. -Control of the posterior lobe The neuroendocrine reflexes control the posterior lobe of the hypophysis. • Sucking infant stimulates nerve endings  hypothalamus  posterior lobe  oxytocin  milk ejection. • Milk ejection reflex can be triggered by a baby's cry. • Emotional stress can affect secretion of gonadotropins, disrupting ovulation, menstruation, and fertility 2- Feedback from Target Organs - Negative feedback Increased target organ hormone levels inhibits release of hormones - Positive feedback Stretching of the uterus increases Oxitocin release, causes contractions, causing more stretching of uterus, etc. until delivery.

14. Hormonal Negative Feedback from Target Organs 4 1 2 3 5 6 The TH also inhibits the release of TRH by the hypothalamus. Thyrotropin-releasing hormone (TRH) Stimulates the metabolism in most cells throughout the body. The TH inhibits the release of TSH by the pituitary. Thyroid-stimulating hormone (TSH) Thyroid hormone (TH)

15. Hormonal Positive Feedback from Target Organs Uterine contractions begin After delivery uterine contractions stop and the cycle ends Oxytocin Uterine contractions Oxytocin

16. Other Endocrine Glands Pineal gland It is attached to roof of third ventricle beneath the posterior end of corpus callosum. • It synthesizes melatonin from serotonin during the night. It synchronizes the physiological function with 24-hour circadian rhythms of daylight and darkness. It may regulate timing of puberty in humans. Thymus It is a bilobed gland in the mediastinum superior to the heart, which goes through involution after puberty. The thymus plays a role in three systems: endocrine, lymphatic, and immune. It is the site of maturation of T cells, which are important in immune defense. It secretes hormones (thymopoietin, thymosin, and thymulin) that stimulate development of other lymphatic organs and activity of T-lymphocytes.

17. The thyroid gland is the largest endocrine gland. It is composed of two lobes and an isthmus below the larynx. The Thyroid Gland Follicle Simple cuboidal epithelium with follicular cells C cells or parafollicular cells Thyroid follicles: Sacs that compose most of thyroid and contain a protein rich colloid. Follicular cells: They secrete thyroxine (T4) and triiodo-thyronine (T3). • Those hormones increase metabolic rate, O2 consumption, heat production (calorigenic effect), appetite, growth hormone secretion, alertness and quicker reflexes. Parafollicular (C) cells: They secrete calcitonin when blood calcium rises. Calcitonin stimulates osteoblast activity and bone formation.

18. The Parathyroid Glands They are four glands partially embedded in posterior surface of thyroid gland. They secrete the parathyroid hormone (PTH) in response to low levels of calcium in blood (hypocalcaemia). The parathyroid hormone (PTH) increases the concentration of Ca2+ in blood by three mechanisms: • 1- Increases the activity of the osteoclasts, which increase bone resorption. • 2- Promotes synthesis of calcitriol in kidneys, which increases absorption of Ca2+ in the intestines. • 3- Decreases urinary excretion of Ca2+

19. Parathyroid hormone is released by parathyroid gland [Calcium] in blood Calcitonin hormone is released by thyroid gland [Calcium] in blood Hormonal Control of Calcium by Thyroid and Parathyroid Glands First Hormonal Mechanism • Increases the activity of the osteoclasts, promotes synthesis of calcitriol in kidneys, and decreases urinary excretion of Ca2+ [Calcium] in blood Second Hormonal Mechanism • Inhibits the activity of the osteoclasts, and stimulates the activity of osteoblasts to deposit Ca2+ [Calcium] in blood

20. The Adrenal Glands They are small glands that sit on top of each kidney. The inner core is the adrenal medulla (10 to 20 % of the gland). The adrenal cortex is thicker (80 to 90 % of the gland). Adrenal gland Connective tissue capsule Kidney Adrenal cortex: Zona glomerulosa Adrenal cortex Zona fasciculata Zona reticularis Adrenal medulla

21. The Adrenal Medulla Adrenal Medulla It has a dual nature acting as an endocrine gland and sympathetic ganglion of sympathetic nervous system. • It consists of modified sympathetic postganglionic neurons called chromaffin cells. • When stimulated, chromaffin cells release catecholamines (epinephrine and norepinephrine) and a trace of dopamine directly into the bloodstream Effects of the Catecholamines Their effect is longer lasting than neurotransmitters. They increases alertness and prepares body for physical activity: • 1- They mobilize high energy fuels, lactate, fatty acids, and glucose. • 2- They increase blood pressure, heart rate, blood flow to muscles, pulmonary air flow and metabolic rate. • 3- They decrease digestion and urine production.

22. The Adrenal Cortex Adrenal cortex It surrounds adrenal medulla and produces more than 25 steroid hormones called corticosteroids or corticoids. • 1- Zona glomerulosa (thin, outer layer) Adrenal cortex • It secretes mineralocorticoids, which regulate the body’s electrolyte balance. • 2- Zona fasciculata (thick, middle layer) • It secretes glucocorticoids, which regulate metabolism of glucose and other fuels. Adrenal medulla • 3- Zona reticularis (narrow, inner layer) • It secretes sex steroids (androgens and estradiol).

23. The Pancreas • It is an exocrine digestive gland, which contains endocrine cell clusters (pancreatic islets). Tail of pancreas Bile duct (c) Pancreatic islet Exocrine acinus Pancreatic ducts Duodenum Head of pancreas Beta cell (a) Alpha cell Delta cell (b) Pancreatic islet

24. Alpha cells (a cells) • They secret glucagon, which is released between meals when blood glucose concentration is falling in liver. Alpha cell Glucagon is a hyperglycemic hormone because increases glucose level in blood by three mechanisms: 1- It stimulates gluconeogenesis (formation of glucose from other compounds), 2- It stimulates glycogenolysis (breaking down of glycogen to release glucose Beta cell Delta cell 3- It stimulates the release of glucose into the circulation raising blood glucose level Beta cells (b cells) They secret insulin during and after meal when glucose and amino acid blood levels are rising. • Insulin is a hypoglycemic hormone because lowers glucose level in blood by three mechanisms: • 1- It stimulates cells to absorb glucose and store or metabolize it. • 2- It promotes synthesis glycogen, fat, and protein from glucose. • 3- It suppresses use of already stored fuels other than glucose. • Insufficiency or inaction of insulin is cause of diabetes mellitus.

25. Delta cells (d cells) They secret somatostatin, which: • 1- Partially suppresses secretion of glucagon and insulin. • 2- Inhibits nutrient digestion and absorption which prolongs absorption of nutrients. PP cells or F cells • They secret pancreatic polypeptide, which inhibits gallbladder contraction and secretion pancreatic digestive enzymes. G cells They secret gastrin, which stimulates stomach acid secretion, motility and emptying.

26. The Gonads The ovaries and testes are both endocrine and exocrine. • The exocrine products are whole cells: the eggs and the sperm. • The endocrine products are the gonadal hormones, mostly steroids. • After ovulation, the remains of the follicle becomes the corpus luteum, which secretes progesterone for 12 days following ovulation. The Ovaries • Follicle and corpus luteum secrete inhibin, which suppresses FSH secretion from anterior pituitary. The theca cells synthesize androstenedione, which is converted to mainly estradiol by theca and granulosa cells. • Functions of Estradiol and Progesterone: • 1- Development of female reproductive system and physique including adolescent bone growth. • 2- Regulate menstrual cycle, and sustain pregnancy. • 3- Prepare mammary glands for lactation.

27. The Testes • Microscopic seminiferous tubules produce sperm. • Tubule walls contain sustentacular(Sertoli) cells, which produce inhibin. Inhibin limits FSH secretion in order to regulate sperm production. • Leydig cells (interstitial cells) lie in clusters between tubules. They produce testosterone and other steroids. Functions of Testosterone: • 1- It stimulates development of male reproductive system in fetus and adolescent, and sex drive. • 2- It sustains sperm production.