Chapter 18

1. Chapter 18 Anatomy & Physiology Fifth Edition Seeley/Stephens/Tate (c) The McGraw-Hill Companies, Inc.

2. Review of the mechanisms of hormonal action • The action of hormone is usually by activation of cytosolic enzymes. • But, first, the hormones identify the target cells by the receptors on the membrane (epinephrine, NE, peptide hormones) or in the cytoplasm (steroid hormones) or the nucleus ( thyroid hormones). • The hormones which attack the target receptors on the membrane do not usually permeate through the membrane. These are first messengers. • The first messenger binds the receptor on the membrane and triggers the release of the second messenger.

3. Hormone-receptor-release of cyclic AMP-activation of adenylate cyclase – ATP becomes cyclic-AMP. • Cyclic –AMP can activate enzymes specific to a cell. • One hormone can also have an effect on many different types of cells. • Other second messengers are Ca++ and c-GMP. • Thyroid and steroid hormones have effects directly on the nucleus or indirectly through cytosol. • These hormones affect protein synthesis e.g. anabolic steroid hormone.

4. Control of Endocrine Activity • The regulation of endocrine activity with the hypothalamus is a good example of how the nervous system and endocrine system integrate. • In addition, the activity of endocrine cells may be in response to its environment by negative feedback. • For ex: • Circulating Ca++ levels goes down- parathyroid hormone is released – target cell elevates Ca++ level- increased Ca++ level- releases calcitonin – lowered Ca++ level.

5. The Pituitary Gland • This small hypophysis (pituitary gland) • Located under the hypothalamus, excretes 9 major peptides hormones which are regulated by hypothalamus and exhibits profound effects on many tissues and organs. • The structure 1 cm in diameter 0.5 1.0 g Sits on the sella turcica of the sphenoid bone connected to hypothalamus through Infundibulum. Divided into: (18.2) • Posterior Pituitary (neurohypophysis) lobe • Anterior Pituitary (adenohypophysis) lobe

7. Posterior Pituitary • Developmentally it is an extension of the brain. • Releases neurohormones. • Anterior Pituitary • Developmentally traces back to the oral cavity called Rathke’s pouch. • Divided into three distinctive areas: • The pars tuberalis • The pars distalis • The pars intermedia • Release regular hormones

9. Regulation of Pituitary by Hypothalamus (18.3) • In the region where the pituitary connects with the hypothalamus and the anterior pituitary, there are two capillary networks: • Hypothalamohypophyseal portal system as the primary capillary network. • Secondary capillary network in the anterior pituitary. • The neurohormone released from the hypothalamus enter the primary capillary. • The hormones are carried into the secondary capillary and are released into anterior pituitary. • These hormones may either increase or inhibit the excretion of hormones from the anterior pituitary. • Hormones from the anterior pituitary, then will be carried by the circulatory system. • Note the number of neurohormones released from the hypothalamus that effect the anterior pituitary gland (Table 18.1). Most of them are small peptides.

11. As for the posterior pituitary, there is no connecting portal system. • The neurosecretory cells from the hypothalamus extend to the posterior pituitary through hypothalamohypophyseal tract. • The neurohormones will be released into the portal system of the posterior pituitary.

15. Hormones of the Pituitary Glands • They are mostly peptides, proteins or glycoproteins. • Posterior pituitary hormones: • The posterior pituitary stores and releases two polypeptide neurohormones formed in the hypothalamus and transmitted through hypothalamohypophyseal nerve tract. • Antidiuretic hormone (ADH): prevents production of large quantity of urine (kidneys) It is also vasopressin and constricts blood vessels. • Oxytocin: stimulates the smooth muscle cells of the uterus. Important for expulsion of fetus, also ejection of milk during lactation, and during intercourse. Does the posterior pituitary gland make its own hormone?

17. Anterior Pituitary Hormones • Hormones secretion is regulated by the neurohormones from the hypothalamus. • Growth hormone (protein): targets may cells and over all increase in metabolism. • Thyroid-stimulating hormone (glycoprotein): targets the thyroid gland and increases thyroid hormone release. • Adrenocorticotropic hormone (peptide): targets the adrenal cortex and increase glucocorticoid hormone secretion. • Note the others in Table 18.2

19. Tropic hormones : are hormones which stimulate or regulate the secretion of hormones from other endocrine glands. • Among the anterior pituitary hormones: • Thyroid-stimulating hormone (TSH) is a glycoprotein: targets the thyroid gland and increase thyroid hormone (TH) release. • Adrenocorticotropic hormone (ACTH) is a peptide: targets the adrenal cortex and increase glucocorticoids hormone secretion.

20. The Thyroid Gland • Located at the upper portion of the trachea. • Structure: • Consist of two lobes connected by a narrow band of tissue called isthmus. • Hormones of the thyroid • The follicular cells of the thyroid gland release derivates of tyrosine to which three or four iodine molecules are attached, thus, • triiodothyronine (T3) makes up ~ 10% • Tetraiodothyronine (T4) makes up ~ 90%, also known as thyroxine. • Parafollicular cells release calcitonin.

23. Synthesis and release of thyroid hormones • Thyroid hormone synthesis requires thyroid stimulating hormone (TSH) from the anterior pituitary and iodine. For further details you may refer to figure 18.8. • Secretion of thyroid hormone is initiated by TSH. (18.9) but it stares with the release of TRH from the hypothalamus, to the hypothalamohypophyseal portal system of the anterior pituitary, where TSH is released. TSH reaches the thyroid gland through the circulatory system and regulate the secretion of T3 and T4.

25. Transporting Thyroid Hormones • Thyroid hormones are transported through the circulatory system bound with thyroxin-binding globulin (TBG). The binding helps the half-life of the hormones to increase to 1 week in the circulatory system. During this period thyroxin (T4) may convert to (T3), which is the more active form. • The Targets of Thyroid Hormones • Thyroid hormones affect many cells, but not exactly in the same manner. They affect metabolism, growth and maturation. They permeate through the membrane and bind with the receptors in the nuclei to react with the DNA for protein synthesis. • Thyroid hormone may interact with mitochondria and produce more ATP and hence heat production. • It requires about 1 week for the thyroid hormones to take affect.

27. The action of thyroid hormones • The effects of thyroid hormones are numerous and listed in Table 18.4. Some examples are: • Hypersecretion: increased metabolic rate, high body temperature, weight loss, increased appetite, rapid heart rate etc….. • Hyposecretion; decreased metabolic rate, low body temperature, weight gain, loss of appetite, reduced heart rate etc…. • Essential for the normal growth of children.

28. Calcitonin • Produced from the parafollicular cells. • Increased level of Ca++ stimulates the release of calcitonin from parafollicular cells. • Target is bone tissue and deceases osteoclast activity, thus increases the life span of osteoblast. (negative feedback) • Therefore, blood calcium levels may be regulated with calcitonin. • Decreases blood levels of calcium.

29. Parathyroid Glands • The location • The small packed parathyroid glands are located in the posterior part of each lobe of the thyroid gland. • The hormone of the parathyroid gland is a peptide. • Targets and function • The gland detects blood Ca++ levels. • PTH regulates calcium levels and targeted to bone, the kidneys and the intestines. • PTH stimulates, for example • Osteoclast activity in bone tissue • Induces Ca++ reabsorption in the kidneys to increase enzyme activity to form vitamin D • Increased Ca++ absorption by small intestines. • Inactive parathyroid glands result in hypocalcaemia (low blood Ca++)

31. For further homeostasis by PTH you may refer to Fig.18.11 • Calcitonin & PTH are antagonistic

33. Adrenal Glands • Location • The adrenal glands are attached on top of the kidney and may be divided, based on the embryonic origin, into outer adrenal cortex and inner adrenal medulla. (18.12) • Histology (in the lab) • Hormones of the Adrenal Medulla • Two major hormones of amino acids derivatives • Epinephrine (adrenaline) – 80% • Norepinephrine (noradrenaline) – 20% • Norepinephrine is a precursor to epinephrine.

34. As shown in Fig 18.13, in the hypothalamus stimulation by stress, physical activities, low blood glucose levels triggers generation of action potential through the sympathetic division of its ANS. The stimuli release either N or NE from the adrenal medulla. • The results of stimulation are: • Increased release of glucose from liver • Increased released of fatty acids from fat store • Increased heart rate • Increased constriction of visceral blood vessels (inc. blood pressure.)

35. Hormones of the Adrenal Cortex • Three types: mineralocorticoids, glucocorticoids, and androgens (Table 18.7) • These lipid soluble steroids are gradually released from the cells as they are made and upon binding with specific plasma proteins, they are distributed through the circulatory system. • Their target organs and functions are described in Table 18.7.

38. Pancreas • Location and structure • Located behind the peritoneum between the greater curvature of the stomach and the duodenum • 15 cm long and weighs 85-100g. • Histology • Has both exocrines and endocrines • The exocrine portion consists of Acini that produce pancreatic juice and a duct system. • The endocrine part consists of pancreatic islets (islets of Langerhans) separated into: • Alpha cells (glucagon production) • Beta cells (insulin production) • Delta cells (somatostatin)

40. Hormones of the pancreas • Insulin is a protein, glucagon is a polypeptide, and somatostatin is a peptide. • Insulin: produced in beta cells in response to rising blood glucose and amino acids. Targets the liver, adipose tissue, muscles the hypothalamus. • Insulin binds to the receptor on the membrane and stimulates glucose transport into the cell. Glucose, once inside the cell, is metabolized to make energy, glycogen, amino acids, proteins, fats etc… Glucose uptake by the liver (glycogen synthesis) and brain cells is independent of insulin.

41. Glucagon • Secreted from alpha cells when blood glucose levels fall. • In the liver, it stimulates glycogenelysis (glycogen hydrolysis) and releases glucose into circulation. • In adipose tissue it initiates breaking down of fats and releases free fatty acids and ketone bodies. • It also responds to blood amino acids after high protein meal.

42. Somatostatin • Produced in delta cells of islets when blood glucose and amino acids rise after a meal. • It behaves as a paracrine secretion ( chemical messenger that diffuses to neighboring target cells, I.e.alpha and beta cells. • Thus modulates their activities. • Regulation of Pancreatic Hormones • The level of nutrients in blood. • ANS also controls insulin secretion. • See Fig. 18.17 for response to a meal.

47. The Pineal Body • At the roof of thalamus. • Produces melatonin and arginine vasotocin. • Collateral from the visual pathways enter the pineal body and effect melatonin production. • Melatonin is made mostly at night. • Melatonin (decrease GnRH) and vasotocin secretions may act on the gonads to inhibit reproductive functions

49. Exert from Clinical Focus on Diabetes Mellitus • Patients with Diabetes Mellitus have difficulty in controlling their blood sugar level. The causes are attributed to: • Inability to make insulin by pancreatic islet cells. Target cells lack membrane receptor for insulin on the cells of target tissues. • The first type is called insulin dependent diabetes mellitus (IDDM), since the patients may be treated with insulin, or Type I diabetes. It accounts for about 3% of the total diabetes population. It is assumed that the cause is related to the loss of insulin production by pancreatic islets, possibly due to an autoimmune disease. The patients are primarily children.

50. The second type is called non-insulin dependent diabetes mellitus (NIDDM), since insulin does not improve the condition of the patients, or Type II diabetes. It accounts for 97% of the total diabetes population. The target cells of insulin appear to have diminished ability to produce insulin receptors, thus the effect of insulin is declined. The patients are mostly adults and sometimes the disease is referred to as adult on set diabetes. Genetic link is suspected. (REVIEW CLINICAL FOCUS ON DIABETES)