1. Chapter 18 -2
Endocrine Glands

2. Comparison of neuronal and endocrine as communication channels
The neuronal system:
Has clear pathways which are connected with neurons. Thus it is reasonably clear for each neuron where it starts and where it ends.
At the end, knob, a neurotransmitters is released.
Its complexity makes it possible to stimulate more than one tissue and organs simultaneously.
The effect is relatively short lived.

5. Chemical Signals
Intercellular: Allow one cell to communicate with other cells as hormones
Autocrine
Released by cells and have a local effect on same cell type from which chemical signals released as prostaglandin
Paracrine
Released by cells and affect other cell types locally without being transported in blood as somatostatin
Pheromones
Secreted into environment that modify behavior and physiology as sex pheromones

6. Chemical Structure of Hormones

7. Control of Secretion Rate
Most hormones are not secreted at constant rate
Patterns of regulation
Involves action of substance other than hormone on an endocrine gland
Involves neural control of endocrine gland
Involves control of secretory activity of one endocrine gland by hormone or neurohormone secreted by another endocrine gland

8. 3. Control of secretion rate
In essence the control is in a form of negative feedback. Three major patterns:
a. By other substance; Such as sugar control the regulation of insulin release.
Increased blood sugar Stimulates insulin release from the pancreas Insulin stimulates glucose uptake by tissues
Results in decreased blood sugar

9. There are three major types of hormone structures: (Table 17.2 and Fig. 17.3)
i. Amino acid derivatives: Epinephrine, Norepinephrine, the thyroid hormones, pineal hormone (melatonin)
ii. Peptide/protein hormone: Antidiuretic hormone, glucagon, oxytocin, growth hormone, prolactin, insulin.
iii. Lipid derivatives: a. Steroid hormones. Estrogens, testosterone, b. Prostaglandins. Derived from arachidonic acid.

10. REVIEW of the mechanisms of hormonal action
The action of hormone is usually by activation of cytosolic enzymes or DNA.
But, first, the hormones identify the target cells by the receptors on the membrane (epinephrine, Norepinephrine, 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.

11. The first messenger binds the receptor on the membrane and triggers the release of the second messenger.
Hormone - receptor - release of cyclic AMP - activation of adenylate cyclase - ATP becomes cyclic-AMP
Cyclic-AMP can activate enzymes specific to a cell.
Thus, one hormone can have effect on many different types of cells.
Other second messengers are Ca++ and cyclic-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.

12. 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 (Fig. 18-5).

14. In addition, the activity of endocrine cells may be in response to its environment by negative feedback. For example: If circulating Ca++ levels go down - Parathyroid hormone is released - Target cell elevates Ca++ level - Increased Ca++ level - Releases Calcitonin - lowered Ca++ level

15. Always prepare to ask:
Where is the gland found?
How does it look like?
What stimulates the gland?
What hormone does it release?
What is the target organ(s)?
Ultimately, what does it do?

16. Endocrine System Functions
Metabolism and tissue maturation
Ion regulation
Water balance
Immune system regulation
Heart rate and blood pressure regulation
Control of blood glucose and other nutrients
Control of reproductive functions
Uterine contractions and milk release

17. Pituitary Gland and Hypothalamus Note the direction of the face
Where nervous and endocrine systems interact
Pituitary gland/hypophysis
Secretes 9 major hormones
Hypothalamus
Regulates secretory activity of pituitary gland through neurohormones and action potentials
Posterior pituitary is an extension of the hypothalamus

18. Pituitary Gland Structure
Posterior or neurohypophysis
Continuous with the brain
Secretes neurohormones
Anterior or adenohypophysis
Consists of three areas with indistinct boundaries: pars distalis, pars intermedia, pars tuberalis

19. This small hypophysis (pituitary gland): (Fig
This small hypophysis (pituitary gland): (Fig. 18-6) is located under the hypothalamus, excretes 9 major peptide hormones which are regulated by hypothalamus and exhibits profound effects on many tissue and organs. a. The Structure I cm in diameter g Sits on the sella turcica of the sphenoid bone Connected to hypothalamus through infundibulum. Divided into Posterior pituitary (neurohypophysis) Anterior pituitary (adenohypophysis)

20. b. Posterior Pituitary Developmentally, it is an extension of the brain Releases neurohormones c. 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 Releases endocrine hormones

21. d. Regulation of pituitary by hypothalamus i
d. Regulation of pituitary by hypothalamus i. The anterior pituitary (Fig. 18-7)

22. In the region pituitary connects with hypothalamus and anterior pituitary, there are two capillary networks: Hypothalamohypophyseal portal system as the primary capillary network Secondary capillary network in anterior pituitary. Neurohormones released from hypothalamus enter the primary capillary. The hormones carried to the secondary capillary and 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.

23. Note the number of neurohormones released from the hypothalamus that affect the anterior pituitary gland. (Fig. 18-8a,b) Most of them are small peptides

26. ii. The posterior pituitary (Fig 18-7) 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.

27. Hypothalamus, Posterior Pituitary Gland

28. Pituitary Gland Hormones Mostly peptides, proteins or glycoproteins.
Posterior
Antidiuretic hormone (ADH)
Oxytocin
Anterior
Growth hormone (GH) or somatotropin
Thyroid-stimulating hormone (TSH)
Adrenocorticotropic hormone (ACTH)
Melanocyte-stimulating hormone (MSH)
Luteinizing hormone (LH)
Follicle-stimulating hormone (FSH)
Prolactin

30. Anterior Pituitary Hormones Hormone secretion is regulated by the neurohormones from the hypothalamus. Growth hormone GH (protein): Targets many cells and over all increase in metabolism. Control of GH secretion is shown in Seeley’s Fig

31. Growth Hormone (GH)
Stimulates uptake of amino acids and conversion into proteins
Stimulates breakdown of fats and glycogen
Promotes bone and cartilage growth
Increased secretion in response to increase amino acids, low blood glucose, or stress
Regulated by GHRH and GHIH or somatostatin

32. Thyroid-stimulating hormone TSH (glycoprotein): Targets the thyroid gland and increase thyroid hormone release Adrenocorticotropic hormone ACTH (peptide): Targets the adrenal cortex and increase glucocorticoid hormone secretion. These hormone, which stimulate release of hormones from other endocrine glands are called “tropic hormones”

33. The gonadotropins include follicle-stimulating hormone, luteinizing hormone and prolactin and regulate activity of gonads. They are under regulation of gonadotropin releasing hormone (GnRH) from the hypothalamus. Follicle-stimulating hormone promotes follicle development in females and together with LH stimulates release of estrogens. In males FSH stimulates sustentacular cell formation. FSH production is inhibited by inhibin. Luteinizing hormone induces ovulation, promotes secretion of the estrogens and the progesterone. More later. Prolactin stimulates mammary gland development, milk production.

34. ii. 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. It is also vasopressin and constricts blood vessels. Control of ADH secretion is shown in Seeley’s Fig Oxytocin: stimulates the smooth muscle cells of the uterus. Important for expulsion of the fetus. Milk ejection. Question: Does the posterior pituitary gland make its own hormone?

35. Antidiuretic Hormone Also called vasopressin
Promotes water retention by kidneys
Secretion rate changes in response to alterations in blood osmolality and blood volume
Lack of ADH secretion is a cause of diabetes insipidus

36. Oxytocin Promotes uterine contractions during delivery
Causes milk ejection in lactating women

37. Thyroid Gland One of largest endocrine glands Highly vascular
Histology
Composed of follicles
Parafollicular cells
Secrete calcitonin which reduces calcium concentration in body fluids when levels elevated

38. Hormones of the thyroid The follicular cells of the thyroid gland (Fig
Hormones of the thyroid The follicular cells of the thyroid gland (Fig ) release derivatives of tyrosine to which three or four iodine molecules are attached, thus triiodothyronine (T3)-10% tetraiodothyronine (T4)-90% - thyroxine. Parafollicular cells (Fig. 18.7b,c) release calcitonin.

39. Thyroid Hormones Include Transported in blood
Triiodothryronine or T3
Tetraiodothyronine or T4 or thyroxine
Transported in blood
Bind with intracellular receptor molecules and initiate new protein synthesis
Increase rate of glucose, fat, protein metabolism in many tissues thus increasing body temperature
Normal growth of many tissues dependent on

40. Synthesis of T3 and T4 Thyroid hormone synthesis requires thyroid stimulating hormone (TSH) from the anterior pituitary and iodine. (Fig a)

42. Secretion of thyroid hormone is initiated by TSH. (Fig
Secretion of thyroid hormone is initiated by TSH. (Fig b and Seeley Fig ) In fact, it starts with a 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.

44. Regulation of T3 and T4 Secretion

45. 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

46. f. 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 effect.

48. Thyroid Hormone Hyposecretion and Hypersecretion
Hypothyroidism
Decreased metabolic rate
Weight gain, reduced appetite
Dry and cold skin
Weak, flabby skeletal muscles, sluggish
Myxedema
Apathetic, somnolent
Coarse hair, rough dry skin
Decreased iodide uptake
Possible goiter
Hyperthyroidism
Increased metabolic rate
Weight loss, increased appetite
Warm flushed skin
Weak muscles that exhibit tremors
Exophthalmos
Hyperactivity, insomnia
Soft smooth hair and skin
Increased iodide uptake
Almost always develops goiter

49. Parafollicular cells and Calcitonin Increased level of Ca++ stimulates the release of calcitonin from the Parafollicular cells. The target is bone tissue and decreases osteoclast activity, thus increases the life span of osteoblasts. Thus decreases blood Ca++ and phosphates.
Therefore, blood calcium level may be regulated with calcitonin.

50. Parathyroid Glands Embedded in thyroid Secrete PTH
Increases blood calcium levels
Stimulates osteoclasts
Promotes calcium reabsorption by kidneys

51. Targets and Function Parathyroid hormone (PTH) regulates calcium levels and targeted to bone, the kidneys and the intestine. The action is opposite to calcitonin PTH stimulates, for example Osteoclast activity in bone tissue leading to bone resorption and the release of calcium and phosphate, i.e. increased blood Ca++ (,but not necessarily phosphate). Induces Ca++ reabsorption in the kidneys to increase enzyme activity to form vitamin D. Inactive parathyroid glands, due to lack of Ca++ increase in blood by PTH, lead to hypocalcemia - nervousness, spasm, etc.

53. Adrenal Glands Functions as part of sympathetic nervous system
Composed of medulla and cortex (3 layers)
Hormones
Medulla secretes epinephrine and norepinephrine
Cortex secretes mineralocorticoids, glucocorticoids, androgens

55. Hormones of Adrenal Cortex
Mineralocorticoids
Zona glomerulosa
Aldosterone produced in greatest amounts
Increases rate of sodium reabsorption by kidneys increasing sodium blood levels
Glucocorticoids
Zona fasciculata
Cortisol is major hormone
Increases fat and protein breakdown, increases glucose synthesis, decreases inflammatory response
Androgens
Zona reticularis
Converted to androgen and testosterone

57. Pancreas Located along small intestine and stomach Exocrine gland
Produces pancreatic digestive juices
Endocrine gland
Consists of pancreatic islets
Composed of
Alpha cells secrete glucagon
Beta cells secrete insulin
Delta cells secrete somatostatin

59. The exocrine portion consists of Acini that produces pancreatic juice (enzymes) and a duct system. The endocrine part consists of pancreatic islets (islets of Langerhans) separated into:
Alpha cells (glucagon production, protein)
Beta cells (insulin production, polypeptide).
Delta cells (somatostatin, peptide)
F Cells (pancreatic polypeptide PP)

60. c. Hormones of the pancreas (Table 18-6) Insulin is a protein, glucagon is a polypeptide, and somatostatin is a peptide.
i. 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 cells. Glucose, once inside the cell, is metabolized to make energy, glycogen, amino acids, proteins, fats, etc.
Glucose uptake by the kidneys, lining of digestive tracts, red blood cells and brain cells is independent of insulin.

61. ii. Glucagon Secreted from alpha cells when blood glucose levels fall
ii. Glucagon Secreted from alpha cells when blood glucose levels fall. In the liver, it stimulates glycogenolysis (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.

62. iii. 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.

63. Insulin and Glucagon Insulin
Target tissues: liver, adipose tissue, muscle, and satiety center of hypothalamus
Increases uptake of glucose and amino acids by cells
Glucagon
Target tissue is liver
Causes breakdown of glycogen and fats for energy

65. Regulation of Blood Nutrient Levels After a Meal

66. Regulation of Blood Nutrient Levels During Exercise

67. Hormones of the Reproductive System - more later
Female: Ovaries
Estrogen and Progesterone
Uterine and mammary gland development and function, external genitalia structure, secondary sex characteristics, menstrual cycle
Inhibin
Inhibits FSH secretion
Relaxin
Increases flexibility of symphysis pubis
Male: Testes
Testosterone
Regulates production of sperm cells and development and maintenance of male reproductive organs and secondary sex characteristics
Inhibin
Inhibits FSH secretion

68. Pineal Body In epithalamus Produces Melatonin Arginine vasotocin
Enhances sleep
Arginine vasotocin
Regulates function of reproductive system in some animals

69. b. The kidneys The kidneys release the steroid hormone calcitriol, the peptide hormone erythropoietin and the enzyme rennin. Erythropoietin Released from kidney when oxygen level is low. Simulate synthesis of erythrocytes in the bone marrow.

70. Calcitriol In response to PTH, cholecalciferol (Vitamin D3) is formed in the skin under the sun and eventually becomes calcitriol. Calcitriol stimulates calcium and phosphate absorption, stimulates Ca++ release from bone, and inhibits PTH secretion. See Fig and Table 18-7 for details. Renin Response to the loss in renal blood flow rein-angiotensin system is activated (See Fig b)

74. Effects of Aging on Endocrine System
Gradual decrease in secretory activity of some glands
GH as people age
Melatonin
Thyroid hormones
Kidneys secrete less renin
Familial tendency to develop type II diabetes

75. Diabetes Mellitus
Results from inadequate secretion of insulin or inability of tissues to respond to insulin
Types
Type I or IDDM (Insulin-dependent)
Develops in young people
Type II or NIDDM (Non-insulin dependent)
Develops in people older than 40-45
More common

76. Patients with Diabetes Mellitus have difficulty in controlling their blood sugar level. The causes are attributed to:
Inability to make insulin by the pancreatic islet cells – Type I, IDDM
Lack of membrane receptor for insulin on the cells of target tissues. – Type II, NIDDM

77. 1. 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 auto-immune disease.
The patients are primarily children.

78. 2. 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 adult and sometime the disease is referred to as adult on set diabetes.
Genetic linkage is suspected.

79. In addition to glucose tolerant test and others, chronic severity of the disease may be assessed by the level of HbAIC, which is a glucose bound (glycated) hemoglobin.
Glucose binds to hemoglobin spontaneously and the degree of bound glucose is proportional to the level of blood glucose, since glucose permeates the membrane of red blood cells almost freely.
Thus, the higher the concentration of blood glucose the higher the percentage of HbAIC The value could go as high as 15% compared with 2-3% of the normal subject.