-
1. Describe the anatomical relationships between the hypothalamus and the pituitary.
- The pituitary gland, or hypophysis, lies in a pocket of the sphenoid bone (called the sella turcica) at the
- base of the brain, just below the hypothalamus. The pituitary gland is connected to the hypothalamus
- by the infundibulum, or pituitary stalk, containing axons from neurons in the hypothalamus and small
- blood vessels. In humans the pituitary gland is composed of two adjacent lobes—the anterior lobe
- usually referred to as the anterior pituitary gland or adenohypophysis and the posterior lobe usually
- called the posterior pituitary gland or neurohypophysis.
- The posterior pituitary is not actually a gland, but rather an extension of the neural components of
- the hypothalamus. The axons of the hypothalamic supraoptic and paraventricular nuclei pass down the
- infundibulum and end within the posterior pituitary in close proximity to capillaries. The axon
- terminals release hormones into these capillaries, which then collect into veins and the general
- circulation.
- The anterior pituitary is connected to the hypothalamus not by neural connections but by an
- unusual blood vessel connection. The capillaries in the median eminence at the base of the
- hypothalamus recombine to form the hypothalamo-pituitary (or hypothalamo-hypophyseal) portal
- vessels. They pass down the infundibulum connecting the hypothalamus and pituitary and enter the
- anterior pituitary where they drain into a second capillary bed, the anterior pituitary capillaries. Thus,
- the hypothalamo-pituitary portal vessels offer a local route for blood flow directly from the
- hypothalamus to the cells of the anterior pituitary.
-
2. Name the two posterior pituitary hormones and describe their site of synthesis and
- mechanism of release.
- Oxytocin and vasopressin (also known as antidiuretic hormone or ADH). These hormones are
- synthesized in the cell bodies of the neurons (one type of hormone per neuron) that form the supraoptic
- and paraventricular nuclei within the hypothalamus, and are then packaged into small vesicles, which
- move down the axon by axon transport to accumulate in the axon terminals of the posterior pituitary
- gland. Various stimuli activate inputs to these neurons, causing action potentials that propagate to the
- axon terminals and trigger the release of the stored hormone by exocytosis. The hormone then enters
- capillaries in the posterior pituitary to be carried away by blood returning to the heart.
-
3. List all six well-established anterior pituitary hormones and their major functions.
- (1) Growth hormone (GH, somatotropin): Stimulates body growth, primarily by stimulating the
- secretion of insulin-like growth factor I (IGF-I) by target cells; also has direct effects on protein,
- carbohydrate, and lipid metabolism.
- (2) Thyroid-stimulating hormone (TSH, thyrotropin): Stimulates the growth of the thyroid gland and
- the secretion of thyroxine and triiodothyronine.
- (3) Adrenocorticotropic hormone (ACTH, corticotropin): Stimulates growth of the adrenal cortex and
- secretion of cortisol by that gland.
- (4) Prolactin: Stimulates breast growth and development and milk synthesis; may be permissive for
- certain reproductive functions in the male.
- (5 and 6) Follicle-stimulating hormone (FSH) and luteinizing hormone (LH)— collectively, the
- gonadotropins. They stimulate development of the gonads, the secretion of sex steroids by the gonads,
- and gamete production in them. These effects occur in both sexes, but the names are derived from some
- specific functions in females.
-
4. List the major hypophysiotropic hormones and the hormone whose release each controls.
- (1) Growth hormone-releasing hormone (GHRH): Stimulates secretion of GH.
- (2) Somatostatin (SS): Inhibits secretion of GH.
- (3) Thyrotropin-releasing hormone (TRH): Stimulates secretion of TSH.
- (4) Corticotropin-releasing hormone (CRH): Stimulates secretion of ACTH.
- (5) Gonadotropin-releasing hormone (GnRH): Stimulates secretion of both gonadotropins FSH and
- LH.
- (6) Dopamine (DA): Inhibits secretion of prolactin.
-
5. What kinds of inputs control the secretion of the hypophysiotropic hormones?
- Some of the neurons that secrete hypophysiotropic hormones may have spontaneous activity. In
- addition, neurons of the hypothalamus receive stimulatory and inhibitory synaptic input from
- virtually all areas of the CNS, and specific neural pathways influence secretion of the individual
- hypophysiotropic hormones. A large number of neurotransmitters are released at the synapses on the
- hormone-secreting hypothalamic neurons, which explains why the secretion of hypophysiotropic
- hormones can be altered by drugs that influence these neurotransmitters.
- One example of neural control of hypophysiotropic hormone secretion is the increased secretion of
- CRH in response to a wide variety of physical and emotional stresses that act via neural pathways to
- the hypothalamus. Other neural control of CRH comes from the circadian-rhythm generator (see
- Chapter 1).
- The secretion of the hypophysiotropic hormones is also controlled by negative feedback exerted
- upon the hypothalamus by one or more of the hormones in the hypothalamo-anterior pituitary-target
- gland sequence. For example, rising levels of cortisol reduce the secretion of CRH by causing a decrease
- in the frequency of action potentials in the neurons secreting CRH.
-
6. Diagram the CRH-ACTH-cortisol system.
Figure 11-19
-
7. What is the difference between long-loop and short-loop negative feedback in the
- hypothalamo-anterior pituitary system?
- Long-loop negative feedback refers to the inhibitory effects exerted by the third hormone in a
- hypothalamo-anterior pituitary-target gland sequence (e.g., cortisol) on the secretion of the
- hypophysiotropic hormone (e.g., CRH) and the anterior pituitary gland hormone (e.g., ACTH). Shortloop
- negative feedback refers to the inhibitory effects (generally) of an anterior pituitary gland hormone
- on the secretion of the hypophysiotropic hormone that stimulates its secretion. (The case of prolactin is
- special because increased plasma levels of prolactin stimulate dopamine secretion. But because
- dopamine is inhibitory to prolactin secretion, the effect is one of negative feedback.)
-
1. Describe the steps leading to T3 and T4 production, beginning with the transport of iodide
- into the thyroid follicular cell.
- Synthesis of thyroid hormones begins when circulating iodide is cotransported with Na+ across the
- follicular cell plasma membrane. Once inside the follicular cell, the bulky iodide cannot diffuse back
- into the interstitial fluid; this is known as iodide-trapping. The trapped, negatively charged iodide ions
- diffuse down their electrical and concentration gradients to the lumenal border of the follicular cells.
- Inside of the colloid of the follicles, iodide is oxidized to iodine and attached to the phenolic rings of
- tyrosine molecules within the amino acid structure of the protein thyroglobulin by the enzyme thyroid
- peroxidase. Within the lumen of the follicle (in the colloid), additional diiodotyrosines are added to
- tyrosine residues on the thyroglobulin. If two diiodotyrosines are bound, the product is T4. If a
- monoiodotyrosine and a diidotyrosine are attached, the product is T3. When thyroid hormone is
- required in the blood, the thyroglobulin re-enters the follicular cell by endocytosis. Lysosomal enzymes
- then cleave molecules of T3 and T4, which diffuse out of the cell and into the blood.
-
2. What are the major actions of TSH on thyroid function and growth?
- TSH stimulates the synthesis of T3/T4. It also stimulates protein synthesis in follicular cells, increases
- DNA replication and cell division, and increases the amount of rough endoplasmic reticulum and
- other cellular machinery required by the follicular cells for protein synthesis.
-
3. What is the major way in which the TRH/TSH/TH pathway is regulated?
- TRH from the hypothalamus stimulates the secretion of TSH from the anterior pituitary gland which
- stimulates the secretion of T3 and T4 from the thyroid gland. T3 and T4 inhibit the secretion of TRH
- and TSH through long-loop and short-loop negative feedback mechanisms, respectively.
-
4. Explain why the symptoms of hyperthyroidism may be confused with a disorder of the
- autonomic nervous system.
- A permissive action of T3 and T4 is to up-regulate beta-adrenergic receptors in many tissues, notably
- the heart and nervous system. Thus, symptoms of excess thyroid hormone concentration closely
- resemble some of the symptoms of excess epinephrine and norepinephrine (sympathetic nervous system
- activity). Although catecholamine levels are normal, they have a greater effect on target tissues in
- patients with hyperthyroidism because of the potentiating effect of increased T3 and T4.
-
5. Explain how both hypothyroidism and hyperthyroidism can result in the appearance of a
- goiter.
- A goiter develops if there is higher than normal stimulation of TSH receptors located within the
- thyroid gland. In primary hypothyroidism, there is no negative feedback to the anterior pituitary so
- TSH levels are elevated, and the excessive stimulation of the TSH receptors causes a goiter to develop.
- If the hyperthyroidism is caused by Graves' disease, antibodies stimulate the TSH receptor (even
- though actual TSH levels are lower than normal) causing the same effects as TSH itself; one of which
- is a goiter.
-
1. Diagram the CRH-ACTH-cortisol pathway.
Figure 11-19
-
2. List the physiological functions of cortisol.
- Cortisol has permissive actions on the reactivity to epinephrine and norepinephrine of smooth
- muscle cells that surround blood vessels such as arterioles. Partly for this reason, therefore, basal
- levels of cortisol help maintain normal blood pressure. Cortisol is also important for maintaining
- the cellular concentrations of certain enzymes involved in metabolic homeostasis. These key
- enzymes are mostly in the liver, and they act to increase hepatic glucose production between
- meals, thereby preventing plasma glucose levels from significantly decreasing below normal. Antiinflammatory
- and anti-immune actions are also essential functions of cortisol. Finally, during
- fetal and neonatal life, cortisol is an important developmental hormone. It has been implicated in
- the proper differentiation of numerous tissues and glands, including various parts of the brain, the
- adrenal medulla, the intestine, and the lungs.
-
3. Define stress, and list the functions of cortisol during stress.
- Stress is an environmental change that must be adapted to if health and life are to be maintained.
- It is an event that elicits cortisol secretion.
- (1) Cortisol affects organic metabolism in many ways. In general, it increases the amount of
- substrates available for energy metabolism. These include proteolysis in bone, lymph, muscle, and
- elsewhere, lipolysis in adipose tissue causing the release of glycerol and free fatty acids into the
- blood, amino acid uptake and gluconeogenesis in the liver, and maintenance of plasma glucose
- levels by insulin antagonism.
- (2) Cortisol causes enhanced vascular reactivity.
- (3) Cortisol causes inhibition of inflammation and adaptive immune responses.
- (4) Cortisol inhibits nonessential functions such as reproduction and growth.
- (5) Cortisol has unidentified protective effects against the damaging influences of stress.
-
4. Contrast the symptoms of adrenal insufficiency and Cushing’s syndrome.
- In adrenal insufficiency, cortisol levels are chronically lower than normal. This may be caused by
- destruction of the adrenal gland by disease (primary adrenal insufficiency) or because of a failure
- of the pituitary gland to secrete ACTH (secondary adrenal insufficiency). Adrenal insufficiency
- results in low blood pressure due to the loss of cortisol's permissive effects on the blood vessels. If a
- patient has primary adrenal insufficiency and the levels of aldosterone are also decreased, then the
- inability to retain salt and water can also lead to hypotension. Blood sugar levels are low because
- of the loss of cortisol's effects on organic metabolism.
- On the other hand, cortisol excess, possibly caused by a hormone-producing tumor of the
- adrenal gland or the anterior pituitary gland, is known as Cushing’s syndrome. Hypertension is
- often a symptom because of cortisol's permissive effect on the blood vessels. Hyperglycemia,
- muscle weakness, osteoporosis, and thinning of the skin can occur due to the excess breakdown
- and mobilization of organic molecules. Immunosuppression is brought about by cortisol excess.
- Cushing’s syndrome is often associated with loss of fat mass from the extremities, and with a
- redistribution of the fat in the trunk, face, and back of the neck. It can also lead to an increased
- appetite.
-
5. List the major effects of activation of the sympathetic nervous system during stress.
- (1) increased glycogenolysis in muscle and liver, (2) increased breakdown of adipose tissue
- triglyceride, (3) increased cardiac function including an increased heart rate, (4) redistribution of
- blood from the viscera to skeletal muscle by means of vasoconstriction in the former beds and
- vasodilation in the latter, (5) increased lung ventilation by stimulating brain breathing centers
- and dilating airways
-
1. Describe the process by which bone lengthens.
- Linear bone growth occurs at the ends, or epiphyses, of the bone. Chondrocytes within a region of
- actively proliferating cartilage called the epiphyseal growth plate continuously produce new
- cartilage. Osteoblasts along the shaft-side of the growth plate convert the cartilage to bone and
- push the epiphyseal plate away from the shaft resulting in growth.
-
2. What are the effects of malnutrition on growth?
- Proper nutrition is a requirement for growth. Sufficient levels of amino acids, fatty acids,
- vitamins, and minerals must be present not only during childhood but also during prenatal
- development. Improper nutrition will stunt growth.
-
3. List the major hormones that control growth.
- (1) growth hormone (which primarily works indirectly through the actions of the mitogen IGF-1),
- (2) insulin-like growth factor I, (3) insulin-like growth factor II, (4) T3 and T4, (5) insulin,
- (6) testosterone, (7) estradiol, (8) cortisol.
-
4. Describe the relationship between growth hormone and IGF-1 and the roles of each in
- growth.
- Growth hormone is secreted by the anterior pituitary gland where it enters the bloodstream and
- acts on many tissues. In some tissues like muscle, growth hormone directly stimulates protein
- synthesis. In bones, growth hormone acts directly on prechondrocytes in the epiphyseal plate to
- differentiate into mature chondrocytes. However, many of the effects of growth hormone are
- mediated indirectly through the actions of insulin-like growth factor I (IGF-1). After growth
- hormone stimulates chondrocytes to mature, they begin to secrete IGF-1 and also become sensitive
- to it. IGF-1 works in a paracrine or autocrine manner to stimulate cell division. Besides its role in
- promoting bone growth, growth hormone also plays a role in energy homeostasis. It does this in
- part by facilitating the breakdown of triglycerides that are stored in adipose cells, which then
- release fatty acids into the blood. It also stimulates gluconeogenesis in the liver, and inhibits the
- ability of insulin to promote glucose transport into certain cells. Growth hormone, therefore, tends
- to increase circulating energy stores.
-
5. What are the effects of growth hormone on protein synthesis?
- Growth hormone stimulates protein synthesis especially in skeletal muscle. It does this by
- increasing amino acid uptake and both the synthesis and activity of ribosomes, all of which are
- essential for protein synthesis.
-
6. Give two ways in which short stature can occur.
- Short stature can occur because of a lack of growth hormone secretion by the anterior pituitary
- gland. It can also be caused by an inability to produce IGF-1 or an insensitivity of target tissues to
- IGF-1.
-
7. What is the status of growth hormone secretion at different stages of life?
- Growth hormone levels are moderate in children, peak during adolescence and are lowest during
- adulthood.
-
8. State the effects of the thyroid hormones on growth.
- Thyroid hormones are essential for normal growth. They are required for both the synthesis and
- the growth-promoting effects of growth hormone.
-
9. Describe the effect of testosterone on growth, cessation of growth, and protein synthesis.
- Which of these effects does estrogen also exert?
- Testosterone promotes growth by stimulating the secretion of growth hormone and IGF-1.
- Testosterone also induces closure of the epiphyseal plates and thus stops growth. These effects are
- shared by estrogens. Testosterone alone has the added ability to stimulate protein synthesis in
- nonreproductive organs and tissues of the body.
-
10. What is the effect of cortisol on growth?
- In high concentrations, cortisol inhibits growth by inhibiting DNA synthesis and promoting
- protein catabolism in many organs. Cortisol also inhibits bone formation and growth hormone
- secretion.
-
1. Describe bone remodeling.
- Throughout life, bone is being constantly remodeled by the combined actions of osteoblasts—the boneforming
- cells that secrete collagen to form a surrounding matrix called osteoid, which then becomes
- calcified—and osteoclasts—the cells that break down (resorb) previously formed bone by secreting
- hydrogen ions, which dissolve the crystals of calcium, phosphate, and hydroxyl ions, and hydrolytic
- enzymes, which digest the osteoid. In remodeling, osteoclasts resorb old bone, and then osteoblasts
- move into the area and lay down new matrix, which becomes mineralized. Osteoblastic activity is
- stimulated by the stresses imposed on bone by gravity and muscle tension. It is also affected by many
- hormones and a variety of autocrine/paracrine growth factors produced locally in bone.
-
2. Describe the handling of Ca2+ by the kidneys and the gastrointestinal tract.
- About 60 percent of plasma Ca2+ is filterable at the renal corpuscle (the rest is bound to plasma
- proteins), and most of this filtered Ca2+ is reabsorbed. There is no tubular secretion of Ca2+. The control
- of Ca2+ excretion is exerted mainly on reabsorption; that is, reabsorption is reflexly decreased when
- plasma Ca2+ goes up, and reflexly increased when plasma Ca2+ goes down.
- In contrast to the absorption of almost 100 percent of ingested Na+, K+, and water from the
- gastrointestinal tract, a considerable amount of ingested Ca2+ is not absorbed. Moreover, the active
- transport system that achieves Ca2+ absorption is under important hormonal control. Accordingly,
- there can be large regulated increases or decreases in the amount of Ca2+ absorbed from the diet.
- Hormonal control of this absorptive process is the major means for homeostatically regulating totalbody
- calcium balance, more important than the control of renal Ca2+ excretion.
-
3. What controls the secretion of parathyroid hormone, and what are this hormone’s major
- effects?
- Parathyroid hormone secretion is controlled by the extracellular Ca2+ concentration acting directly on
- the secretory cells via a plasma membrane Ca2+ receptor of the parathyroid glands. Decreased plasma
- Ca2+ concentration stimulates parathyroid hormone secretion, and an increased plasma Ca2+
- concentration does the opposite.
- Parathyroid hormone:
- (1) Directly increases the reabsorption of bone by osteoclasts, which results in the movement of
- calcium (and phosphate ions) from bone into extracellular fluid.
- (2) Directly stimulates the formation of 1,25-dihydroxyvitamin D, which then increases the intestinal
- absorption of calcium (and phosphate ions). Thus, the effect of parathyroid hormone on the intestinal
- tract is indirect.
- (3) Directly increases tubular Ca2+ reabsorption in the kidneys, thereby decreasing urinary Ca2+
- excretion.
- (4) Directly reduces the tubular reabsorption of phosphate ions in the kidneys, thus increasing its
- urinary excretion. This keeps plasma phosphate ions from increasing at a time when parathyroid
- hormone is simultaneously causing increased release of both calcium and phosphate ions from bone and
- when 1,25-dihydroxyvitamin D is increasing both calcium and phosphate ion absorption in the
- intestine.
-
4. Describe the formation and action of 1,25-(OH)2D. How does parathyroid hormone influence
- the production of this hormone?
- The term vitamin D denotes a group of closely related compounds. Vitamin D3 is formed in the body
- by the action of ultraviolet radiation on 7-dehydrocholesterol in the skin. Another form of vitamin D
- that is very similar to vitamin D3 is ingested in food (vitamin D2). Both forms must be activated by
- the addition of two hydroxyl groups. The first addition occurs in the liver by the enzyme 25-
- hydroxylase and results in the formation of 25-hydroxyvitamin D3. The second addition occurs in
- certain kidney tubule cells by the enzyme 1-hydroxylase and results in the active form of the
- hormone—1,25-dihydroxyvitamin D (1,25-(OH)2D). The major action of 1,25-(OH)2D is to
- stimulate absorption of Ca2+ by the intestine.
- Parathyroid hormone stimulates the enzyme (1-hydroxylase) that catalyzes the second
- hydroxylation step that occurs in the kidneys
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