The Endocrine Physiology The Pituitary Gland

1. The Endocrine PhysiologyThe Pituitary Gland Dr. Khalid Alregaiey

2. Learning Objectives • List the functional parts (lobes) of the pituitary gland. • Describe the relationships of the hypothalamus to the anterior and posterior pituitary glands. • Describe the hypothalamo-hypophyseal portal system. • Explain the physiological significance of the hypothalamo-hypophyseal portal system in regulating anterior pituitary functions. • List the hypothalamic hormones and their target cells in the anterior pituitary. • List the anterior pituitary hormones and their target tissues. • Summarize the functions of the anterior pituitary hormones. • Outline the different feedback loops regulating secretion of anterior pituitary hormones. • Summarize the direct and indirect physiological actions of growth hormone. • Outline neuroendocrine control of growth hormone secretion • List stimuli that increase and decrease growth hormone secretion • Describe the role of prolactin in milk secretion. • Discuss regulation of prolactin secretion.

3. Hypothalamus • hypothalamus is located at the base of the brain. It is part of the limbic system, which controls the autonomic nervous system and the endocrine systems. • One of the most important functions of the hypothalamus is to link the nervous system to the endocrine system via the pituitary gland (hypophysis). • Secretes releasing hormones to cause the pituitary to release hormones • Secretes inhibiting hormones to turn off secretion of pituitary hormones

4. Three Methods of Hypothalamic Control over the Endocrine System

5. Hormones of the Hypothalamus

6. Pituitary (Hypophysis) • pituitary gland, also called the hypophysis, is a small gland—about 1 cm in diameter and 0.5 to 1 gram in weight— that lies in the sella turcica, a bony cavity at the base of the brain, and is connected to the hypothalamus by the pituitary (or hypophysial) stalk.

7. Pituitary (Hypophysis) • Neurohypophysis – posterior lobe (neural tissue) and the infundibulum • Receives, stores, and releases hormones from the hypothalamus • Adenohypophysis – anterior lobe, made up of glandular tissue • Synthesizes and secretes a number of hormones

8. The Anatomy and Orientation of the Pituitary Gland

9. Pituitary-Hypothalamic Relationships: Anterior Lobe • The anterior lobe of the pituitary is an outpocketing of the oral mucosa • There is no direct neural contact with the hypothalamus • There is a vascular connection, the hypophyseal portal system,

10. Hypophyseal portal system • At the median eminence, terminals of hypothalamic neurons release regulatory factors into the tissue fluids then taken by fenestrated capillaries down to the anterior lobe. • Releasing hormones • Inhibiting hormones • All blood entering the portal system will reach the intended target cells before returning to the general circulation

11. The Hypophyseal Portal System

12. Pituitary (Hypophysis)

13. Pituitary-Hypothalamic Relationships: Posterior Lobe • Has a neural connection with the hypothalamus (hypothalamic-hypophyseal tract) • Nuclei of the hypothalamus (supraoptic and paraventricular) synthesize oxytocin and antidiuretic hormone (ADH) • These hormones are transported to the posterior pituitary

14. Cells Types of the Anterior Pituitary • Five cell types in the anterior pituitary: 1. Somatotropes—human growth hormone (hGH) 2. Corticotropes—adrenocorticotropin (ACTH) 3. Thyrotropes—thyroid-stimulating hormone (TSH) 4. Gonadotropes—gonadotropic hormones, which include both luteinizing hormone (LH) and folliclestimulating hormone (FSH) 5. Lactotropes—prolactin (PRL)

15. Adenophypophyseal Hormones • The six hormones of the adenohypophysis: • Are abbreviated as GH, TSH, ACTH, FSH, LH, and PRL • Regulate the activity of other endocrine glands • In addition, pro-opiomelanocortin (POMC): • Has been isolated from the pituitary • Is enzymatically split into ACTH, opiates, and MSH

16. Adenohypophyseal Cells & Hormones Cell Hormone Chemistry Physiologic Actions Single chain of 39 amino acids Glycoprotein having two subunits,  (89 amino acids) and ß (112 amino acids) Glycoprotein having two sub- units,  (89aa) and ß (115aa) Glycoprotein having two sub- units,  (89aa) and ß (115aa) Single chain of 198 amino acids Single chain of 191 amino acids Adrenocorticotropic hormone (cortico- tropin; ACTH) Thyroid-stimulating hormone (thyro- tropin; TSH) Follicle-stimulating hormone (FSH) Lutenizing hormone (LH) Prolactin (PRL) Growth hormone (somatotropin; GH) Stimulates production of glucocorticoids and androgens by the adrenal cortex; maintains size of zona fasciculata and zona reticularis of cortex Stimulates production of thyroid hormones,T4 and T3, by thyroid follicular cells;maintains size of follicular cells Stimulates development of ovarian follicles; regulates spermatogenesis in the testis Causes ovulation and formation of corpus luteum in the ovary; stimulates production of estrogen and progesterone by the ovary; stimulates testosterone production by the testis Essential for milk production by lactating mammary gland Stimulates postnatal body growth; stimulates secretion of IGF-1; stimulates triglyceride lipolysis; inhibits actions of insulin on carbo- hydrate and lipid metabolism Corticotropes Thyrotropes Gonadotropes Gonadotropes Mammotropes, Lactotropes Somatotropes

17. Growth Hormone (GH) • growth hormone (GH) is a protein hormone secreted by somatotropes (somatotrophs), which make up around 40% of the anterior pituitary gland. • GH has many target tissues including bone, skeletal muscle, liver and adipose tissue.

18. Growth Hormone (GH) • Antagonistic hypothalamic hormones regulate GH • Growth hormone–releasing hormone (GHRH) stimulates GH release • Growth hormone–inhibiting hormone (GHIH) inhibits GH release

19. Growth hormone promotes growth of many body cells • Promote increased size of the cells • Increased mitosis • Specific differentiation of certain types of cells such as bone growth cells and early muscle cells

20. Indirect physiological role of GH (GH and growth) • Mechanism of action of IGF-1: • Increases amino acids uptake by chondrocyres. • Stimulates protein synthesis by chondrocyres. • Stimulates mitosis of chondrocytes. This effect causes an increase in number of chondrocytes (i.e., hyperplasia). • Stimulates expansion in size of the chondrocytes (i.e., hypertrophy). • Thus, IGF-1 leads to elongation of the bones.

21. Growth hormone has several metabolic effects 1- Increased rate of proteins synthesis in most cells of the body 2- Increased mobilization of fatty acids from adipose tissue, increased free fatty acid in the blood, and increased use of fatty acids for energy. 3- Decreased rate of glucose utilization through the body

22. Increased rate of proteins synthesis in most cells of the body (anabolic effect) GH promotes protein deposition in tissues : • enhancement of amino acid transport through the cell membrane • enhancement of RNA translation to cause protein synthesis by the ribosomes • Increased nuclear transcription of DNA to form RNA • Decreased catabolism of protein and amino acids

23. Increased Mobilization of Fatty Acids • release of fatty acids from adipose tissue • increasing the FFA in the body fluids • conversion of FFA to acetyl coemzyme A • fat is used for energy in preference to the use of carbohydrates and proteins. • High GH levels might cause excessive fat mobilization leading to acetoacetic acid formation by the liver>>> causing ketosis>>>fatty liver.

24. Decreased rate of glucose utilization through the body (decrease carbohydrate utilization) • Decreased glucose uptake in tissues such as skeletal muscle and fat • Increased glucose production by the liver • increased insulin secretion (cause insulin resistance). • Excess secretion of growth hormone =metabolic disturbances very similar to patients with type II diabetes. (diabetogenic effect)

25. Necessity of insulin and carbohydrate for the growth promoting action of growth hormone • Animal +lacks of pancreas>>>>no growth hormone effect • Animal+ diet without carbohydrate >>>> no growth hormone effect • Carbohydrate and insulin>>production of energy • Insulin : transport of amino acids into cells and glucose transport stimulation

26. Growth hormone stimulates cartilage and bone Growth • Increased deposition of protein by the chondrocytic and osteogenic cells that cause bone growth • Increased rate of reproduction of these cells • Converting chondrocytes into osteogenic cells, thus causing deposition of new bone • Strongly stimulates osteoblast activity.

27. Somatomedins (insulin Like Growth factor-1) • Chondrocytes cultured outside the body+ growth hormone= proliferation or enlargement fails. • Growth hormone +inside body= proliferation and growth of cells

28. Factors Affecting GH Secretion Stimulation Inhibition Glucose decrease Free fatty acid decrease Amino acid increase (arginine) Fasting Prolonged caloric deprivation Stress Exercise Puberty Androgens and estrogens Sleep Somatostatin Glucose increase Free fatty acid increase IGF-1 Growth hormone Senescence

29. Metabolic vs. Growth actions of Growth Hormone • Metabolic actions of growth hormone are directly induced by the GH through its receptor. • Growth actions are mediated by insulin-like growth factor 1 (IGF-1)

30. Metabolic Action of Growth Hormone

31. Hyposecretion of GH; Dwarfism • Dwarfism means failure in growth (i.e., growth retardation). • It is caused usually by defective HGH axis (hypothalamic-anterior pituitary-liver-target organs axis). • Thus, dwarfism can be caused by decreased secretion of GHRH, HGH or IGF-I. There may be a defect in the GH receptors. • Other causes of dwarfism include deficiency of thyroid hormones in childhood.

32. Hyposecretion of GH; Dwarfism Normal and abnormal growth

33. Hypersecretion of HGH Gigantism and acromegaly • Excessive production of GH from a GH-secreting pituitary tumour (somatotropes tumours)can cause gigantism if excessive GH production occurs when the body is growing (in childhood and at puberty), i.e., before the epiphyseal growth plates fuse. • Tumors in adulthood (after epiphyseal closure) cause acromegaly.

34. Pituitary gigantism

35. Acromegaly Clinical features: Excessive soft tissue growth 1- prominent supraorbital ridge. 2- Prognathism. 3- Ride-spaced teeth (widening of incisor spaces). 4- Increase shoe size. 5- Thick spade-like hands 6- Deepening voice. 7- Macroglossia. Before After

36. Prolactin (PL) • Prolactin (PL) is secreted from mammotrophs (lactotrophs) in the anterior pituitary. • Control of PL secretion: • Hypothalamic control of PL secretion is performed primarily by dopamine. Thus, pituitary stalk lesions cause hyperprolacinaemia. • The hypothalamic PRH (prolactin releasing hormone), also called prolactin releasing factor (PRF) stimulates release of PL ? The hypothalamic TRH stimulates release of PL. • PL secretion is increased during pregnancy and suckling. • PL causes increased PIH (dopamine) secretion, i.e., it inhibits its own secretion.

37. Prolactin (PL) • Main target organ: • Mammary gland (breast). • Effects in females: • PL plays an important role in the normal development (growth) of the mammary gland and milk synthesis (production) during lactation. • PL inhibits GnRH, FSH and LH secretion. • PL antagonizes the actions of FSH and LH. Thus, ovulation is often inhibited by breast feeding. • Effects in males: • In males, PL is involved in testicular function.

38. Effects of PL and control of its secretion

39. Thyroid Stimulating Hormone (Thyrotropin) • Tropic hormone that stimulates the normal development and secretory activity of the thyroid gland • Triggered by hypothalamic peptide thyrotropin-releasing hormone (TRH) • Rising blood levels of thyroid hormones act on the pituitary and hypothalamus to block the release of TSH

40. The hypothalamic-pituitary-thyroid axis • Thyrotropin releasing hormone (TRH) is produced in the hypothalamus. It reaches the thyrotrophs in the anterior pituitary by the hypothalamic-hypophysial-portal system. • TRH stimulates the synthesis and release of TSH by the thyrotrophs from the anterior pituitary. • In both the hypothalamus and the pituitary, it is primarily T3 that inhibits TRH and TSH secretion, respectively.

41. The hypothalamic-pituitary-adrenal axis • Corticotropin-releasing hormone or factor (CRH or CRF) is produced ) is produced in the hypothalamus. • It reaches the corticotrophs in the anterior pituitary by the hypothalamic-hypophysial-portal system. • CRH stimulates the synthesis of adrenocorticotrophic hormone (ACTH). • ACTH stimulates the synthesis of adrenal steroid hormones. • Glucocorticoids (cortisol) released into the systemic circulation exert negative feedback inhibition of CRF and ACTH release from the hypothalamus and pituitary, respectively.

42. Gonadotropins • Gonadotropins – follicle-stimulating hormone (FSH) and luteinizing hormone (LH) • Regulate the function of the ovaries and testes • FSH stimulates gamete (egg or sperm) production • Absent from the blood in prepubertal boys and girls • Triggered by the hypothalamic gonadotropin-releasing hormone (GnRH) during and after puberty

43. Functions of Gonadotropins • In females • LH works with FSH to cause maturation of the ovarian follicle • LH works alone to trigger ovulation (expulsion of the egg from the follicle) • LH promotes synthesis and release of estrogens and progesterone

44. Functions of Gonadotropins • In males • LH stimulates interstitial cells of the testes (Leydig cells) to produce testosterone • FSH targets Sertoli cells in the seminiferous tubules of the testes and promotes spermatogenesis