ENDOCRINE GLANDS

NERMİN ÖZCAN

Introduction:

The multiple activities of the cells, tissues, and organs of the body are coordinated by the interplay of several types of chemical messenger systems:

NeurotransmittersEndocrine hormonesNeuroendocrine hormonesParacrinesAutocrinesCytokines

The endocrine hormones are carried by the circulatory system to cells throughout the body, including the nervous system in some cases, where they bind with receptors and initiate many reactions.

The multiple hormone systems play a key role in regulating almost all body functions, including metabolism, growth and development, water and electrolyte balance, reproduction, and behavior.

For instance, without growth hormone, a person would be a dwarf. Without thyroxine and triiodothyronine from the thyroid gland, almost all the chemical reactions of the body would become sluggish, and the person would become sluggish as well. Without insulin from the pancreas, the body’s cells could use little of the food carbohydrates for energy. And without the sex hormones, sexual development and sexual functions would be absent.

Chemical Structure and Synthesis of Hormones:

There are three general classes of hormones:

1. Proteins and polypeptides, including hormones secreted by the anterior and posterior pituitary gland, the pancreas (insulin and glucagon), the parathyroid gland (parathyroid hormone), and many others.

2. Steroids secreted by the adrenal cortex (cortisol and aldosterone), the ovaries (estrogen and progesterone), the testes (testosterone), and the placenta (estrogen and progesterone).

3. Derivatives of the amino acid tyrosine, secreted by the thyroid (thyroxine and triiodothyronine) and the adrenal medullae (epinephrine and norepinephrine). There are no known polysaccharides or nucleic acid hormones.

Protein and peptide hormones are synthesized on the rough end of the endoplasmic reticulum of the different endocrine cells, in the same fashion as most other proteins.

They are usually synthesized first as larger proteins that are not biologically active (preprohormones) and are cleaved to form smaller prohormones in the endoplasmic reticulum. These are then transferred to the Golgi apparatus for packaging into secretory vesicles.

Secretion of the hormones occurs when the secretory vesicles fuse with the cell membrane and the granular contents are extruded into the interstitial fluid or directly into the blood stream by exocytosis.

Steroid Hormones Are Usually Synthesized from Cholesterol andAre Not Stored.

The chemical structure of steroid hormones is similar to that of cholesterol, and in most instances they are synthesized from cholesterol itself.

Because the steroids are highly lipid soluble, once they are synthesized, they simply diffuse across the cell membrane and enter the interstitial fluid and then the blood.

Amine Hormones Are Derived from Tyrosine.

The two groups of hormones derived from tyrosine, the thyroid and the adrenal medullary hormones, are formed by the actions of enzymes in the cytoplasmic compartments of the glandular cells. The thyroid hormones are synthesized and stored in the thyroid gland and incorporated into macromolecules of the protein thyroglobulin, which is stored in large follicles within the thyroid gland.

Hormone secretion occurs when the amines are split from thyroglobulin, and the free hormones are then released into the blood stream. After entering the blood, most of the thyroid hormones combine with plasma proteins, especially thyroxine-binding globulin, which slowly releases the hormones to the target tissues.

Mechanisms of Action Hormones:

Each receptor is usually highly specific for a single hormone; this determines the type of hormone that will act on a particular tissue. The target tissues that are affected by a hormone are those that contain its specific receptors.

The locations for the different types of hormone receptors are generally the following:

I. In or on the surface of the cell membraneII. In the cell cytoplasmIII. In the cell nucleus.

(1) Steroid hormones, transported bound to plasma carrier proteins, dissociate from their plasma carriers and pass through the plasma membrane of their target cell.

(2) The steroid hormone binds to receptors, which may be in the cytoplasm.

(3) The hormone-bound receptor translocates to the nucleus, where it binds to DNA.

(4) This stimulates genetic transcription, resulting in new mRNA synthesis.

(5) The newly formed mRNA codes for the production of new proteins,

(6) produce the hormonal effects in the target cell.

(1) Thyroxine, carried to the target cell bound to its plasma carrier protein, dissociates from its carrier and passes through the plasma membrane of its target cell.

(2) In the cytoplasm, T4 is converted into T3 (triiodothyronine), which (3) uses binding proteins to enter the nucleus.

(4) The hormone-receptor complex binds to DNA, (5) stimulating the synthesis of new mRNA. (6) The newly formed mRNA codes for the

synthesis of new proteins, which (7) produce the hormonal effects in the target cell.

Pituitary Hormones and Their Control by the Hypothalamus:

Pituitary Gland: Two Distinct Parts–The Anterior and Posterior Lobes.

The pituitary gland, also called the hypophysis, is a small gland about 1 centimeter 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. Physiologically, the pituitary gland is divisible into two distinct portions: the anterior pituitary, also known as the adenohypophysis, and the posterior pituitary, also known as the neurohypophysis.

Six important peptide hormones plus several less important ones are secreted by the anterior pituitary, and two important peptide hormones are secreted by the posterior pituitary.

The hormones of the anterior pituitary play majör roles in the control of metabolic functions throughout the body

Growth hormone (GH, or somatotropin)

Adrenocorticotropic hormone ( ACTH, or corticotropin )

Thyroid-stimulating hormone ( TSH, or thyrotropin )

Prolactin (PRL) Follicle-stimulating hormone

( FSH, or folliculotropin ) Luteinizing hormone ( LH, or luteotropin )

Posterior Pituitary Hormones are synthesized by cell bodies in the Hypothalamus.

A. Antidiuretic hormone (ADH), also called vasopressin, cause decreased excretion of water by the kidneys.

B. Oxytocin in accordance with its name, powerfully stimulates contraction of the pregnant uterus, especially toward the end of gestation. And it causes milk to be expressed from the alveoli into the ducts of the breast so that the baby can obtain it by suckling.

Hypothalamus Controls Pituitary Secretion:

Almost all secretion by the pituitary is controlled by either hormonal or nervous signals from the hypothalamus.

Special neurons in the hypothalamus synthesize and secrete the hypothalamic releasing and inhibitory hormones that control secretion of the anterior pituitary hormones.

Growth Hormone:

Aside from its general effect in causing growth, growth hormone has multiple specific metabolic effects, including

(1) increased rate of protein synthesis in most cells of the body;

(2) increased mobilization of fatty acids from adipose tissue, increased free fatty acids in the blood, and increased use of fatty acids for energy;

(3) decreased rate of glucose utilization throughout the body.

Growth Hormone:

Abnormalities of Growth Hormone Secretion:

Panhypopituitarism This term means decreased secretionof all the anterior pituitary hormones.

DwarfismMost instances of dwarfism result from

generalized deficiency of anterior pituitary secretion during childhood.

GigantismThe acidophilic, growth

hormone–producing cells of the anterior pituitary gland become excessively active

AcromegalyIf an acidophilic tumor occurs after

adolescence the person cannot growtaller, but the bones can become thicker and

the soft tissues can continue to grow.

Thyroid Hormones:

The thyroid gland, located immediately below the larynx on each side of and anterior to the trachea, is one of the largest of the endocrine glands, normally weighing 15 to 20 grams in adults.

The thyroid secretes two major hormones, thyroxine and triiodothyronine, commonly called T4 and T3, respectively. Both of these hormones profoundly increase the metabolic rate of the body.

Complete lack of thyroid secretion usually causes the basal metabolic rate to fall 40 to 50 per cent below normal, and extreme excesses of thyroid secretion can increase the basal metabolic rate to 60 to 100 per cent above normal. Thyroid secretion is controlled primarily by thyroid-stimulating hormone (TSH) secreted by the anterior pituitary gland.

Production and Action of Thyroid Hormones:

tetraiodothyronine ( T 4 ), or thyroxine,

triiodothyronine ( T 3 )

calcitonin

Thyroid Hormones Increase Cellular Metabolic Activity

The thyroid hormones increase the metabolic activities of almost all the tissues of the body. The basal metabolic rate can increase to 60 to 100 per cent above normal when large quantities of the hormones are secreted. The rate of utilization of foods for energy is greatly accelerated.

Although the rate of protein synthesis is increased, at the same time the rate of protein catabolism is also increased. The growth rate of young people is greatly accelerated. The mental processes are excited, and the activities of most of the other endocrine glands are increased.

Feedback Effect of Thyroid Hormone:

Increased thyroid hormone in the body fluids decreases secretion of TSH by the anterior pituitary. When the rate of thyroid hormone secretion rises to about 1.75 times normal, the rate of TSH secretion falls essentially to zero. Almost all this feedback depressant effect occurs even when the anterior pituitary has been separated from the hypothalamus.

Therefore, it is probable that increased thyroid hormone inhibits anterior pituitary secretion of TSH mainly by a direct effect on the anterior pituitary gland itself. Regardless of the mechanism of the feedback, its effect is to maintain an almost constant concentration of free thyroid hormones in the circulating body fluids

Diseases of the Thyroid:

Hyperthyroidism

Thyroid Adenoma

Hyperthyroidism occasionally results from a

localized adenoma (a tumor) that develops in the thyroid

tissue and secretes large quantities of

thyroidhormone

Exophthalmos

The cause of the protruding eyes is edematous swelling of the retro-orbital tissues and degenerative changes in the extraocular muscles.

Diseases of the Thyroid:

Hypothyroidism:

Endemic Colloid Goiter The term “goiter” means a greatly enlarged thyroid gland.

Idiopathic Nontoxic Colloid Goiter

Enlarged thyroid glandssimilar to those of endemic colloid goiter can also occur

in people who do not have iodine deficiency

MyxedemaMyxedema develops in the

patient with almost total lack of thyroid hormone function

CretinismCretinism is caused by extreme hypothyroidism during fetal life,

infancy, or childhood.

Adrenocortical Hormones:

The two adrenal glands, each of which weighs about 4 grams, lie at the superior poles of the two kidneys. Each gland is composed of two distinct parts, the adrenal medulla and the adrenal cortex.

The adrenal medulla, the central 20 per cent of the gland, is functionally related to the sympathetic nervous system; it secretes the hormones epinephrine and norepinephrine in response to sympathetic stimulation.

In turn, these hormones cause almost the same effects as direct stimulation of the sympathetic nerves in all parts of the body.

The zona glomerulosa aldosterone

The zona fasciculata cortisol

corticosterone

adrenal androgens

estrogens

The zona reticularis dehydroepiandrosterone

(DHEA)

androstenedione

Physiologic Stress Increases ACTH

Pain stimuli caused by physical stress or tissue damage are transmitted first upward through the brain stem and eventually to the median eminence of the hypothalamus.

Here CRF is secreted into the hypophysial portal system. Within minutes the entire control sequence leads to large quantities of cortisol in the blood.

Abnormalities of Adrenocortical Secretion:

Hypoadrenalism-Addison’s Disease

Addison’s disease results from failure of the adrenal cortices to produce adrenocortical hormones.

Hyperadrenalism-Cushing’sSyndrome

Hypersecretion by the adrenal cortex causes a complex cascade of hormone effects called

Cushing’s syndrome.

Primary Aldosteronism(Conn’s Syndrome)

Occasionally a small tumor of the zona glomerulosa cells occurs and secretes large amounts of

aldosterone.

Adrenogenital SyndromeAn occasional adrenocortical tumor secretes excessive quantities of androgens that cause

intense masculinizing effects throughout the body.

Insulin, Glucagon and Diabetes Mellitus:

The pancreas, in addition to its digestive functions, secretes two important hormones, insulin and glucagon, that are crucial for normal regulation of glucose, lipid, and protein metabolism.

Although the pancreas secretes other hormones, such as amylin, somatostatin, and pancreatic polypeptide, their functions are not as well established.

The pancreas is composed of two major types of tissues: (1) the acini, which secrete digestive juices into the duodenum, and (2) the islets of Langerhans.

Insulin and Its Metabolic Effects:

Historically, insülin has been associated with “blood sugar,” and true enough, insulin has profound effects on carbohydrate metabolism. Yet it is abnormalities of fat metabolism, causing such conditions as acidosis and arteriosclerosis, that are the usual causes of death in diabetic patients.

Also, in patients with prolonged diabetes, diminished ability to synthesize proteins leads to wasting of the tissues as well as many cellular functional disorders. Therefore, it is clear that insulin affects fat and protein metabolism almost as much as it does carbohydrate metabolism.

Effect of Insulin:

Glucagon and Its Functions:

Glucagon, a hormone secreted by the alpha cells of the islets of Langerhans when the blood glucose concentration falls, has several functions that are diametrically opposed to those of insulin. Most important of these functions is to increase the blood glucose concentration, an effect that is exactly the opposite that of insulin.

The major effects of glucagon on glucose metabolism are (1) breakdown of liver glycogen (glycogenolysis) and (2) increased gluconeogenesis in the liver. Both of these effects greatly enhance the availability of glucose to the other organs of the body.

Glucagon in very high concentrations also (1) enhances the strength of the heart; (2) increases blood flow in some tissues, especially the kidneys; (3) enhances bile secretion; and (4) inhibits gastric acid secretion. All these effects are probably of minimal importance in the normal function of the body.

Diabetes:

Parathyroid Hormone:

The physiology of calcium and phosphate metabolism, formation of bone and teeth, and regulation of vitamin D, parathyroid hormone (PTH), and calcitonin are all closely intertwined.

Extracellular calcium ion concentration, for example, is determined by the interplay of calcium absorption from the intestine, renal excretion of calcium, and bone uptake and release of calcium, each of which is regulated by the hormones just noted.

Parathyroid hormone provides a powerful mechanism for controlling extracellular calcium and phosphate concentrations by regulating intestinal reabsorption, renal excretion, and exchange between the extracellular fluid and bone of these ions.

Excess activity of the parathyroid gland causes rapid absorption of calcium salts from the bones, with resultant hypercalcemia in the extracellular fluid; conversely, hypofunction of the parathyroid glands causes hypocalcemia, often with resultant tetany.

Pathophysiology of Parathyroid Hormone, Vitamin D, and Bone Disease:

HypoparathyroidismWhen the parathyroid glands do not secrete sufficient PTH, the osteocytic reabsorption of

exchangeable calcium decreases and the osteoclasts become almost totally inactive.

Rickets—Vitamin D Deficiency

Rickets occurs mainly in children. It results fromcalcium or phosphate deficiency in the

extracellular fluid, usually caused by lack of vitamin D

Osteoporosis -Decreased

Bone MatrixOsteoporosis is the most common of all bone

diseasesin adults, especially in old age.

Pineal Gland:

The small, cone-shaped pineal gland is located in the roof of the third ventricle of the diencephalon, where it is encapsulated by the meninges covering the brain.

The pineal gland secretes the hormone melatonin.

The Male Hormonal System:

Testosterone, secreted by the Leydig cells located in the interstitium of the testis, is essential for growth and division of the testicular germinal cells, which is the first stage in forming sperm.

Luteinizing hormone, secreted by the anterior pituitary gland, stimulates the Leydig cells to secrete testosterone.

Follicle-stimulating hormone, also secreted by the anterior pituitary gland, stimulates the Sertoli cells; without this stimulation, the conversion of the spermatids to sperm (the process of spermiogenesis) will not occur.

Estrogens, formed from testosterone by the Sertoli cells when they are stimulated by folliclestimulating hormone, are probably also essential for spermiogenesis.

The female hormonal system:

1. A hypothalamic releasing hormone, gonadotropin-releasing hormone (GnRH)

2. The anterior pituitary sex hormones, follicle-stimulating hormone (FSH) and luteinizing hormone (LH), both of which are secreted in response to the release of GnRH from the hypothalamus

3. The ovarian hormones, estrogen and progesterone, which are secreted by the ovaries in response to the two female sex hormones from the anterior pituitary gland

References:

TEXTBOOK of Medical Physiology - Arthur C. Guyton & John E. Hall HUMAN PHYSIOLOGY - Stuart Ira Fox Human Anatomy and Physiology - Nega Assefa & Yosief Tsige Glandulae Endocrinae – Dr. Turan Peştemalcı Endokrin Sistem ve hastalıkları - Uz.Dr.Aydan Ünsal ENDOKRiN SiSTEM – Megep - 720S00026