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
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
*Standard abbreviations for hormones are given in parentheses.
†Peptide refers to both peptides and proteins.
Figure 9–1 Endocrine glands and the hormones secreted by each gland. Refer to Table 9-1 for abbreviations used in this figure.
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.
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.
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.
Mechanisms of hormone action (and their second messengers) include adenylyl cyclase (cAMP), phospholipase C (IP3/Ca2+), steroid hormone mechanism, and the tyrosine kinase mechanism.
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.
Hormones of the anterior lobe are TSH, FSH, LH, ACTH, growth hormone, and prolactin. Hormones of the posterior lobe are ADH and oxytocin.
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.
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).
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.
Oxytocin secretion is stimulated by suckling and is responsible for milk ejection from the lactating breast.
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.
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.
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.
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.
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
2 Nephrogenic Diabetes Insipidus
3 Conn Syndrome
4 Cushing Disease
5 Surgical Hypoparathyroidism
Urinary cyclic AMP
6 Car Accident That Severs the Hypothalamic-Pituitary Stalk
7 Autoimmune Destruction of the Thyroid
Basal metabolic rate
T3 resin uptake
8 21β-Hydroxylase Deficiency
9 Administration of Synthetic Glucocorticoid (Dexamethasone) to a Normal Person
10 Lung Cancer Producing Parathyroid Hormone-Related Peptide (PTH-rp)
11 17α-Hydroxylase Deficiency
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