Physiology 5th Ed.

Chapter 9. Endocrine Physiology

 

The endocrine system, in concert with the nervous system, is responsible for homeostasis. Growth, development, reproduction, blood pressure, concentrations of ions and other substances in blood, and even behavior are all regulated by the endocrine system. Endocrine physiology involves the secretion of hormones and their subsequent actions on target tissues.

A hormone is a chemical substance that is classified as a peptide, steroid, or amine. Hormones are secreted into the circulation in small amounts and delivered to target tissues, where they produce physiologic responses. Hormones are synthesized and secreted by endocrine cells usually found in endocrine glands. Table 9-1 is a list of hormones and their abbreviations, which are used throughout Chapters 9 and 10.

Table 9–1 Commonly Used Abbreviations in Endocrine Physiology

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The classical endocrine glands are the hypothalamus, anterior and posterior lobes of the pituitary, thyroid, parathyroid, adrenal cortex, adrenal medulla, gonads, placenta, and pancreas. The kidney also is considered to be an endocrine gland, and endocrine cells are found throughout the gastrointestinal tract. Table 9-2 summarizes the major hormones, their glands of origin, their chemical nature, and their major actions. Its companion, Figure 9-1, is a pictorial summary of the endocrine glands and their hormonal secretions.

Table 9–2 Summary of Endocrine Glands and Actions of Hormones

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*Standard abbreviations for hormones are given in parentheses.

Peptide refers to both peptides and proteins.

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Figure 9–1 Endocrine glands and the hormones secreted by each gland. Refer to Table 9-1 for abbreviations used in this figure.

HORMONE SYNTHESIS

REGULATION OF HORMONE SECRETION

REGULATION OF HORMONE RECEPTORS

MECHANISMS OF HORMONE ACTION AND SECOND MESSENGERS

HYPOTHALAMIC-PITUITARY RELATIONSHIPS

ANTERIOR LOBE HORMONES

POSTERIOR LOBE HORMONES

THYROID HORMONES

ADRENAL MEDULLA AND CORTEX

ENDOCRINE PANCREAS

REGULATION OF CALCIUM AND PHOSPHATE METABOLISM

SUMMARY

ent The endocrine glands synthesize and secrete hormones, which circulate to their target tissues. Chemically, hormones may be classified as peptides, steroids, or amines. Hormone levels are measured by radioimmunoassay.

ent Peptide hormones are synthesized by transcription of genes to mRNAs and translation of mRNAs to preprohormones. Signal peptides and other peptide sequences are cleaved from preprohormones to form the peptide hormones, which are packaged in secretory granules. Steroid hormones are synthesized from cholesterol in the adrenal cortex, testes, ovaries, and placenta. Amine hormones are derivatives of tyrosine.

ent Hormone synthesis and secretion is regulated by negative and positive feedback mechanisms. Negative feedback is self-limiting; positive feedback is self-augmenting. Hormone receptors are also regulated by increasing (up-regulation) or decreasing (down-regulation) their number or activity.

ent Mechanisms of hormone action (and their second messengers) include adenylyl cyclase (cAMP), phospholipase C (IP3/Ca2+), steroid hormone mechanism, and the tyrosine kinase mechanism.

ent The connection between the hypothalamus and the posterior lobe of the pituitary is neuronal. The cell bodies are in the hypothalamus, and the hormones are secreted from nerve terminals in the posterior lobe of the pituitary. The hypothalamus is connected to the anterior lobe of the pituitary by hypothalamic-hypophysial portal blood vessels.

ent Hormones of the anterior lobe are TSH, FSH, LH, ACTH, growth hormone, and prolactin. Hormones of the posterior lobe are ADH and oxytocin.

ent Growth hormone is required for growth to normal stature and has actions on carbohydrate metabolism, protein synthesis, organ growth, and bone growth. Many of the actions of growth hormone are mediated by somatomedins. In children, a deficiency of growth hormone causes growth retardation. Excess growth hormone causes acromegaly.

ent Prolactin is responsible for breast development and lactogenesis. Prolactin secretion is under tonic inhibition, mediated by dopamine from the hypothalamus. Excess prolactin secretion (e.g., prolactinoma) causes galactorrhea, which can be treated with dopamine agonists (e.g., bromocriptine).

ent ADH is responsible for osmoregulation by increasing water reabsorption in the principal cells of the kidney. ADH secretion is stimulated by increases in serum osmolarity and by decreases in ECF volume. Deficiency of ADH causes diabetes insipidus; excess ADH causes SIADH.

ent Oxytocin secretion is stimulated by suckling and is responsible for milk ejection from the lactating breast.

ent Thyroid hormones are synthesized by thyroid follicular cells. Tyrosines of thyroglobulin are iodinated, yielding MIT and DIT. Coupling of MIT and DIT produces T3 and T4. T4 is activated to T3 in target tissues. The actions of thyroid hormones include increased Na+-K+ ATPase, increased oxygen consumption and BMR, and increased cardiac output. Hyperthyroidism is commonly caused by thyroid-stimulating immunoglobulins (Graves disease) and exhibits weight loss, increased BMR, excess heat production, rapid heart rate, and nervousness. Hypothyroidism exhibits weight gain, decreased BMR, cold intolerance, slowed movements, and lethargy.

ent Adrenocortical steroid hormones are glucocorticoids, mineralocorticoids, and adrenal androgens, all of which are synthesized from cholesterol. Glucocorticoids stimulate gluconeogenesis and have antiinflammatory and immunosuppressive actions. Mineralocorticoids stimulate Na+ reabsorption and K+ and H+ secretion by the kidney. Addison disease is primary adrenocortical insufficiency. Cushing syndrome is overproduction of glucocorticoids. Conn syndrome is overproduction of mineralocorticoids.

ent The islets of Langerhans have three cell types: α, which secrete glucagon; β, which secrete insulin; and δ, which secrete somatostatin. Insulin is the hormone of “abundance” and promotes storage of glucose as glycogen, storage of fatty acids in adipose, and storage of amino acids as protein. Deficiency of insulin is type I diabetes mellitus; insulin resistance of target tissues is type II diabetes mellitus. Glucagon is the hormone of “starvation” and promotes utilization of stored nutrients.

ent Ca2+ homeostasis is controlled by the interplay of bone, kidney, and intestine, and the actions of the hormones PTH, calcitonin, and vitamin D. The function of PTH is to increase serum ionized Ca2+concentration by increasing bone resorption, increasing intestinal Ca2+ absorption, increasing renal Ca2+ reabsorption, and decreasing renal phosphate reabsorption. Hyperparathyroidism is associated with hypercalcemia and hypophosphatemia. Hypoparathyroidism is associated with hypocalcemia and hyperphosphatemia. Vitamin D is converted to its active form, 1,25-dihydroxycholecalciferol, in the kidney. The function of vitamin D is to promote bone mineralization by increasing the Ca2+ and phosphate concentrations in ECF. Its actions are to increase intestinal and renal Ca2+ and phosphate absorption and to increase bone resorption. Deficiency of vitamin D causes rickets in children and osteomalacia in adults.


Challenge Yourself

Each numbered question begins with an endocrine disorder or a disturbance to an endocrine system. The disorder or disturbance is followed by a list of parameters (e.g., blood level of various substances). For each parameter, predict whether it is increased, decreased, or unchanged.

1 Addison Disease

Cortisol

ACTH

Blood glucose

2 Nephrogenic Diabetes Insipidus

ADH

Urine osmolarity

3 Conn Syndrome

Serum K+

Blood pressure

Renin

4 Cushing Disease

ACTH

Cortisol

Blood glucose

5 Surgical Hypoparathyroidism

Serum Ca2+

Serum phosphate

Urinary cyclic AMP

6 Car Accident That Severs the Hypothalamic-Pituitary Stalk

Prolactin

ADH

Serum osmolarity

PTH

7 Autoimmune Destruction of the Thyroid

T4

TSH

Basal metabolic rate

T3 resin uptake

8 21β-Hydroxylase Deficiency

ACTH

Cortisol

Deoxycorticosterone (DOC)

Aldosterone

Dehydroepiandrosterone (DHEA)

Urinary 17-ketosteroids

9 Administration of Synthetic Glucocorticoid (Dexamethasone) to a Normal Person

ACTH

Cortisol

10 Lung Cancer Producing Parathyroid Hormone-Related Peptide (PTH-rp)

Serum Ca2+

PTH

11 17α-Hydroxylase Deficiency

Blood pressure

Blood glucose

DHEA

Aldosterone


SELECTED READINGS

Bell GI, Pictet RL, Rutter WJ, et al: Sequence of human insulin gene. Nature 284:26, 1980.

DeGroot LJ: Endocrinology, 3rd ed. Philadelphia, WB Saunders, 1994.

Gharib SD, Wierman ME, Shupnik MA, et al: Molecular biology of the pituitary gonadotropins. Endocr Rev 11:177, 1990.

Gilman AG: Guanine nucleotide-binding regulatory proteins and dual control of adenylate cyclase. J Clin Invest 73:1, 1984.

Norman A, Roth J, Orci L: The vitamin D endocrine system: Steroid metabolism, hormone receptors, and biological response (calcium-binding proteins). Endocr Rev 3:331, 1982.

Olefsky JM: The insulin receptor: A multifunctional protein. Diabetes 39:1009, 1991.

Tepperman J, Tepperman HM: Metabolic and Endocrine Physiology, 5th ed. Chicago, Year Book, 1987.

Ullrich A, Bell JR, Chen EY, et al: Human insulin receptor and its relation to the tyrosine kinase family of oncogenes. Nature 313:756, 1985.

Unger RH, Dobbs RE, Orci L: Insulin, glucagon, and somatostatin secretion in the regulation of metabolism. Ann Rev Physiol 40:307, 1978.