Handbook of Endocrinology, Second Edition, Volume I

George H. Gass, Harold M. Kaplan

• Publisher: CRC Press
• Year: 2020
• ISBN:
  9781000722857
• Edition: 2
• Topic: Medizin
• Subtopic: Medizinische Theorie, Praxis & Referenz

Stay on top of the rapid changes sweeping endocrinology today with the latest information on important selected topics in The Handbook of Endocrinology. This extensive two-volume text provides an impressive breadth and depth of coverage difficult to find in other sources. After a broad survey of the functions of major endocrine glands, the book launches into detailed reviews of both established and hot, new research areas.
Selected topics include:

Chapter 1

SUMMATION OF BASIC ENDOCRINE DATA

Kathleen A. Jones

CONTENTS

Thyroid Gland

Triiodothyronine and Thyroxine

Calcitonin (Thyrocalcitonin)

Parathyroid Gland

Parathyroid Hormone

Vitamin D

Relationship to Parathyroid Hormone

Thymus Gland

Pineal Gland

Circumventricular Organs

Adrenal Gland

Medulla

Cortex

Pituitary Gland (Hypophysis)

Posterior Lobe (Neurohypophysis)

Anterior Lobe

Kidney Hormones

Renin-Angiotensin System

Erythropoietin (Hemopoietin)

Cardiac Hormones

Atrial Natriuretic Factor

Gastrointestinal Hormones

Cholecystokinin (Pancreozymin)

Gastric Inhibitory Peptide

Gastrin

Motilin

Secretin

Substance P

Vasoactive Intestinal Peptide

Pancreatic Hormones

Insulin

Glucagon

Male Sex Hormones

Androgens

Female Sex Hormones

Estrogens

Progesterone

Relaxin

Inhibin

Placental Hormones

Human Chorionic Gonadotropin

Human Chorionic Somatomammotropin

Appendix I: Quantitative Aspects of Receptor Binding

Appendix II: Table of Normal Reference Laboratory Values

Appendix III: SmithKline Beecham Clinical Laboratories Performing Endocrine Diagnostic Tests

References

THYROID GLAND

TRIIODOTHYRONINE AND THYROXINE

Structure, Development, and Aging

The thyroid is present in all vertebrates. In humans, it has two lobes, connected by an isthmus, on either side of the trachea. It is enervated by parasympathetic and sympathetic fibers, which control only the diameter of the blood vessels they are in. Histologically it is composed mostly of follicles, containing colloid, which is thyroglobulin. There are also parafollicular cells, which produce calcitonin.

The gland begins to develop in the third embryonic week as an evagination of the pharynx and is clearly differentiated in the 15th week, producing thyroxine. The ultimobranchial body from endoderm cells of the sixth pharyngeal pouch is incorporated into the thyroid and produces the parafollicular or C cells. Thyroid tissue is present in all vertebrates.

Marked changes occur in the thyroid with age. Its structure then resembles the gland when it is in a state of hypothyroidism. Connective tissue increases and many follicles are obliterated. The gland is not essential to life, but its functions are.

Classification

The two chief hormones are L-thyroxine (T₄) and 3,5,3’-1-triiodothyronine (T₃). Another is reverse T₃ (rT₃). Thyroglobulin is the storage form and has no hormonal properties per se. Very little thyroglobulin enters the circulation. Calcitonin, secreted by the C cells, will be considered separately. The hormones T₃ and T₄ are glycoproteins.

Biosynthesis

The synthesis starts with iodide, which the thyroid follicles actively take up. The iodide is oxidized to active iodine, which is incorporated into tyrosine. This is followed by peptide linkages, which are glycoproteins called thyroglobulin. Monoiodotyrosine (MIT) and diiodotyrosine then develop. These couple to form T₃ and T₄, although very little rT₃. An enzyme called thyroid peroxidase catalyzes the whole sequence of reactions.

Release

To obtain the release of T₃ and T₄, there is proteolysis of thyroglobulin followed by endocytosis. Thyrotropin-releasing hormone (TRH), which is hypothalamic in origin, stimulates the pituitary to synthesize and release the thyroid-stimulating hormone (TSH). This promotes the uptake of iodide by the thyroid.

Normal Bodily Effects

The effects vary with the specific hormone that is circulating to the cells of the body. The material stored in colloid as thyroglobulin is translocated to the lumen of each thyroid follicle. T₄, which is necessary for life, is the dominant circulatory form and gives rise to most of T₃ and just about all of rT₃. The hormones circulate almost totally bound to proteins. Thyroxine-binding globulin is the major binding protein; it is a glycoprotein-a-globulin. Other binding proteins are albumin and a thyroid-binding albumin.

A major effect is to increase protein synthesis in all bodily tissues. T₃ is about four times as active metabolically as T₄; T₃ has about two-thirds of the biologic activity of the thyroid hormones. There are effects on thermoregulation, food metabolism, growth and development, reproduction, water and electrolyte activities, and neural behavior.

Basis of Bodily Effects

Thyroid-stimulating hormone is involved, from the anterior pituitary. It binds to the membranes of the follicles and stimulates adenylate cyclase, cAMP is produced, but its control over T₃ and T₄ release needs further study. T₃ and T₄ can enter virtually all body cells when unbound.

CALCITONIN (THYROCALCITONIN)

Structure, Development, Aging

Since calcitonin is produced in the thyroid gland, refer to relevant data for the thyroid. The parafollicular cells of the thyroid are the secretory elements for calcitonin. These originate in the neural crest in the fetus. In vertebrate animals there is an origin in the ultimobranchial body. Calcitonin concentration in the plasma reduces with age and is generally lower in women than in men.

Classification

Calcitonin is a single-chain polypeptide, containing 32 amino acids, with a molecular weight of about 3500. There are species differences in the amino acid sequence. This suggests that the specific sequence order determines the characteristic action. Human calcitonin has been synthesized.

Biosynthesis

Calcitonin is produced in the human thyroid gland in parafollicular cells that lie in the interstitial tissue among the thyroid follicles. The precursor of calcitonin is preprocalcitonin, which hydrolyzes to calcitonin and other polypeptides. The gene for calcitonin is transcribed and changed to a different mRNA in the brain, a peptide called calcitonin-gene-related peptide, whose function other than vasodilation is unknown.

Release

Calcitonin secretion and release increase when the thyroid gland is normally perfused with high plasma concentrations of calcium. Potent natural stimulants include gastrin, dopamine, estrogen, β-adrenergic agonists, and other substances. In man, the thymus and parathyroid may secrete some calcitonin. Hypercalcemia may be the major stimulus for calcitonin secretion.

Normal Bodily Effects

Calcitonin decreases circulating calcium and phosphate levels by inhibiting release of these substances from bone to plasma. This is opposite to the action of the parathyroid hormone (PTH; parathormone). Calcitonin is a short-term regulator of calcium ion concentration, whereas PTH is a long-term regulator that more than offsets the calcitonin effects. Thus, overall, the calcitonin control in the human adult is weak. The hormone has a half-life less than one hour and is excreted by the kidneys. Its peak effect is less than one hour. Calcitonin may be effective against hypercalcemia caused by excessive calcium intake. Whether it is essential for development and maintenance of the skeleton is not clear.

Basis of Bodily Effects

The mechanism underlying the effects involves calcitonin receptors in bones and kidneys. The action permitting the decreasing of calcium in plasma is the inhibition of bone resorption induced by cAMP. There is an increase in osteoblastic activity, but this lasts only a few days. The prolonged effect is in preventing the formation of osteoclasts. In the long run, the parathyroids regulate the level of extracellular calcium.

PARATHYROID GLAND

PARATHYROID HORMONE

Structure, Development, and Aging

There are two pairs of parathyroid glands in man. Each is close to the posterior wall of the thyroid glands. The parathyroids are present only in vertebrates. They secrete PTH.

In the fetus at the fifth week the endoderm of the third pharyngeal pouch differentiates into the inferior aspect of the parathyroids. The endoderm of the fourth pharyngeal pouch is the superior aspect.

The parathyroid glands in the adult human are composed mainly of chief and oxyphil cells. The chief cells secrete PTH and persist throughout life.

Classification

The hormone, PTH, is a single-chain polypeptide containing 84 amino acids.

Biosynthesis

PTH is synthesized as a large precursor molecule on the ribosomes. The precursor is transported to the endoplasmic reticulum in which preproparathyroid hormone is enzymatically changed to proparathyroid hormone and the latter is sent to the Golgi apparatus. The resulting definitive hormone is encapsulated into granules, which are released as the ionized calcium in the extracellular fluids is decreased.

Release

It is the level of ionic calcium in the blood that controls hormonal secretion by way of a negative feedback system. The volume of secretion varies inversely with the calcium level.

Normal Bodily Effects

The major effect is to increase the plasma calcium level. About 90% of the calcium in the body is sent to bone, as a calcium phosphate compound. The hormone degrades the bone matrix. Many other hormones are also involved in bone activity, mostly for growth (e.g., growth hormon...