Hormone Structures and Synthesis

Hormones fall into three chemical classes: (1) amines, (2) peptides and proteins, and (3) steroids.

Amine Hormones

The amine hormones are all derivatives of the amino acid tyrosine. They include the thyroid hormones, epinephrine and norepinephrine (produced by the adrenal medulla), and dopamine (produced by the hypothalamus).

Thyroid Hormones The thyroid gland is located in the lower part of the neck wrapped around the front of the trachea (windpipe). It is composed of many spherical structures called follicles, each consisting of a single layer of epithelial cells surrounding an extracellular central space. This space is filled with a glycoprotein called thyroglobulin. The follicles secrete the two iodine-containing amine hormones—

thyroxine (T4) and triiodothyronine (T3) (Figure 10-1), collectively known as the thyroid hormones (TH), Parafollicular cells, which are located between follicles, secrete a third hormone—a peptide called calci-tonin; this hormone does not contain iodine and is not included in the term "thyroid hormones."

Iodine is an essential element that functions as a component of T4 and T3. Most of the iodine ingested in food is absorbed into the blood from the gastrointestinal tract by active transport; in the process it is converted to the ionized form, iodide. Iodide is actively transported from the blood into the thyroid follicular cells. Once in the cells, the iodide is converted back to iodine, which is then coupled to the side chains of tyrosine molecules that had previously been incorporated into thyroglobu-lin precursor. The result is the formation of thyroglobu-lin, which is stored in the central space of the follicles.

During hormone secretion, thyroglobulin is moved into the follicular cells by endocytosis and, after fusion with lysosomes, is digested to release the thyroid

Vander et al.: Human Physiology: The Mechanism of Body Function, Eighth Edition

Principles of Hormonal Control Systems CHAPTER TEN

Principles of Hormonal Control Systems CHAPTER TEN

3, 5, 3', 5'- Tetraiodothyronine (thyroxine, T4) 1 1 O

3, 5, 3', 5'- Tetraiodothyronine (thyroxine, T4) 1 1 O

FIGURE 10-1

Chemical structures of the thyroid hormones, thyroxine and triiodothyronine. The two molecules differ by only one iodine atom, a difference noted in the abbreviations T3 and T4.

FIGURE 10-1

Chemical structures of the thyroid hormones, thyroxine and triiodothyronine. The two molecules differ by only one iodine atom, a difference noted in the abbreviations T3 and T4.

hormones, which cross the cells' plasma membranes to enter the blood. T4 is secreted in much larger amounts than is T3. However, the plasma membranes of many cell types contain enzymes that convert most of this T4 into T3 by removal of one iodine atom, and this constitutes the major source of plasma T3. This is an important point because T3 is a much more active hormone than is T4. Indeed it is likely that T4 has little or no action unless it is converted into T3. Thus, persons with low peripheral deiodination because of defective enzymes can show evidence of thyroid-hormone deficiency even though they have normal or elevated plasma concentrations of T4.

Virtually every tissue in the body is affected by the thyroid hormones. These effects, which are described in Chapter 18, include regulation of oxygen consumption, growth, and brain development and function.

Adrenal Medullary Hormones and Dopamine

There are two adrenal glands, one on the top of each kidney. Each adrenal gland comprises two distinct endocrine glands, an inner adrenal medulla, which secretes amine hormones, and a surrounding adrenal cortex, which secretes steroid hormones. As described in Chapter 8, the adrenal medulla is really a modified sympathetic ganglion whose cell bodies do not have axons but instead release their secretions into the blood, thereby fulfilling a criterion for an endocrine gland.

The adrenal medulla secretes mainly two amine hormones, epinephrine (E) and norepinephrine (NE). Recall from Chapter 8 that these molecules constitute, with dopamine, the chemical family of catecholamines. The structures and pathways for synthesis of the cate-cholamines were described in Chapter 8, when they were dealt with as neurotransmitters. In humans, the adrenal medulla secretes approximately four times more epi-nephrine than norepinephrine. Epinephrine and norepi-nephrine exert actions similar to those of the sympathetic nerves. These effects are described in various chapters and summarized in Chapter 20 in the section on stress.

The adrenal medulla also secretes small amounts of dopamine and several substances other than cate-cholamines, but whether any of these adrenal secretions other than epinephrine and norepinephrine actually serve hormonal functions is unknown. In contrast, as described below, the dopamine secreted by certain cells in the hypothalamus definitely functions as a hormone.

Peptide Hormones

The great majority of hormones are either peptides or proteins. They range in size from small peptides having only three amino acids to small proteins (some of which are glycoproteins). For convenience, we shall follow a common practice of endocrinologists and refer to all these hormones as peptide hormones.

In many cases, they are initially synthesized on the ribosomes of the endocrine cells as larger proteins known as preprohormones, which are then cleaved to prohormones by proteolytic enzymes in the granular endoplasmic reticulum (Figure 10-2). The prohormone is then packaged into secretory vesicles by the Golgi apparatus. In this process, the prohormone is cleaved to yield the active hormone and other peptide chains found in the prohormone. Therefore, when the cell is stimulated to release the contents of the secretory vesicles by exocytosis, the other peptides are cosecreted with the hormone. In certain cases they, too, may exert hormonal effects. In other words, instead of just one pep-tide hormone, the cell may be secreting multiple pep-tide hormones that differ in their effects on target cells.

One more point about peptide hormones: As mentioned in Chapters 7 and 8, many peptides serve as both neurotransmitters (or neuromodulators) and as hormones. For example, most of the hormones secreted by the endocrine glands in the gastrointestinal tract (for example, cholecystokinin) are also produced by neurons in the brain where they function as neurotransmitters.

Steroid Hormones

The third family of hormones is the steroids, the lipids whose ringlike structure was described in Chapter 2. Steroid hormones are produced by the adrenal cortex and the gonads (testes and ovaries) as well as by the placenta during pregnancy. Examples are shown in Figure 10-3. In addition, the hormone 1,25-dihydroxyvitamin D3, the active form of vitamin D, is a steroid derivative.

Cholesterol is the precursor of all steroid hormones. The cells producing these hormones synthesize some of their own cholesterol, but most is provided to them from the plasma, as described in Chapter 18. The many biochemical steps in steroid synthesis beyond cholesterol involve small changes in the molecules and are mediated by specific enzymes. The steroids produced by a particular cell depend, therefore, on the types and concentrations of enzymes present. Because steroids are highly lipid-soluble, once they are synthesized they simply diffuse across the plasma membrane of the

PART TWO Biological Control Systems

Vander et al.: Human Physiology: The Mechanism of Body Function, Eighth Edition

II. Biological Control Systems

PART TWO Biological Control Systems

10. Principles of Hormonal Control Systems

© The McGraw-Hill Companies, 2001

Plasma membrane

Plasma membrane

Cholamine Flowsheet

FIGURE 10-2

Typical synthesis and secretion of peptide hormones. In some cells, the calcium that causes exocytosis is released from the endoplasmic reticulum by action of a second messenger rather than entering from the extracellular fluid.

Adapted from Hedge et al.

Synthesis

Preprohormone Prohormone

Prohormone Hormone

Secretion

Hormone (and any "pro" fragments)

Synthesis

Preprohormone Prohormone

Prohormone Hormone

Secretion

Hormone (and any "pro" fragments)

FIGURE 10-2

Typical synthesis and secretion of peptide hormones. In some cells, the calcium that causes exocytosis is released from the endoplasmic reticulum by action of a second messenger rather than entering from the extracellular fluid.

Adapted from Hedge et al.

steroid-producing cell and enter the interstitial fluid and then the blood where they mainly bind to certain plasma proteins.

The next sections describe the pathways for steroid synthesis by the adrenal cortex and gonads. Those for the placenta are somewhat unusual and are discussed in Chapter 19.

Hormones of the Adrenal Cortex Steroid synthesis by the adrenal cortex is illustrated in Figure 10-4. The five hormones normally secreted in physiologically significant amounts by the adrenal cortex are aldosterone, cortisol, corticosterone, dehydroepiandrosterone (DHEA), and androstenedione. Aldosterone is known

CH2OH

CH2OH

CH2OH

Cortisol

Aldosterone

Cortisol

Aldosterone

C HO

Testosterone Estradiol

FIGURE 10-3

Structures of representative steroid hormones.

C HO

Testosterone Estradiol

FIGURE 10-3

Structures of representative steroid hormones.

as a mineralocorticoid because its effects are on salt (mineral) balance, mainly on the kidneys' handling of sodium, potassium, and hydrogen ions. Cortisol and corticosterone are called glucocorticoids because they have important effects on the metabolism of glucose and other organic nutrients. Cortisol is by far the more important of the two glucocorticoids in humans, and so we shall deal only with it in future discussions. In addition to its effects on organic metabolism (described in Chapter 18), cortisol exerts many other effects, including facilitation of the body's responses to stress and regulation of the immune system (Chapter 20).

Dehydroepiandrosterone (DHEA) and andro-stenedione belong to the class of hormones known as androgens, which also includes the major male sex hormone, testosterone, produced by the testes. All androgens have actions similar to those of testosterone. Because the adrenal androgens are much less potent than testosterone, they are of little physiological significance in the adult male; they do, however, play roles in the adult female, and in both sexes at puberty, as described in Chapter 19. The use of DHEA as a "supplement" is also discussed in Chapter 19.

The adrenal cortex is not a homogeneous gland but is composed of three distinct layers (Figure 10-5). The outer layer—the zona glomerulosa—possesses very high concentrations of the enzymes required to convert corticosterone to aldosterone but lacks the enzymes required for the formation of cortisol and an-drogens. Accordingly, this layer synthesizes and secretes aldosterone but not the other major adrenal cortical hormones. In contrast, the zona fasciculata and zona reticularis have just the opposite enzyme profile. They, therefore, secrete no aldosterone but much cortisol and androgen.

CH2OH

Vander et al.: Human Physiology: The Mechanism of Body Function, Eighth Edition

Principles of Hormonal Control Systems CHAPTER TEN

Principles of Hormonal Control Systems CHAPTER TEN

Corticosterone

Cortisol

Corticosterone

Aldosterone

Cortisol

FIGURE 10-4

Simplified flow sheet for synthesis of steroid hormones by the adrenal cortex; several intermediate steps have been left out. The various steps are mediated by specific enzymes. The five hormones shown in boxes are the major hormones secreted. Dehydroepiandrosterone (DHEA) and androstenedione are androgens—that is, testosterone-like hormones. Cortisol and corticosterone are glucocorticoids, and aldosterone is a mineralocorticoid.

Adrenal Gland Vanders

FIGURE 10-5

Section through an adrenal gland showing both the medulla and cortex, as well as the hormones they secrete. %

FIGURE 10-5

Section through an adrenal gland showing both the medulla and cortex, as well as the hormones they secrete. %

PART TWO Biological Control Systems

Vander et al.: Human Physiology: The Mechanism of Body Function, Eighth Edition

PART TWO Biological Control Systems

Estradiol Synthesis And Adrenal Disease

Secreted by testes

Secreted by ovaries

FIGURE 10-6

Gonadal production of steroids. Only the ovaries have high concentrations of the enzymes (aromatase) required to produce the estrogens estrone and estradiol.

Secreted by testes

Secreted by ovaries

FIGURE 10-6

Gonadal production of steroids. Only the ovaries have high concentrations of the enzymes (aromatase) required to produce the estrogens estrone and estradiol.

In certain disease states, the adrenal cortex may secrete decreased or increased amounts of various steroids. For example, an absence of the enzymes for the formation of cortisol by the adrenal cortex can result in the shunting of the cortisol precursors into the androgen pathway. In a woman, the result of the large increase in androgen secretion would be masculinization, in addition to the effects of cortisol deficiency (Chapter 20).

Hormones of the Gonads Compared to the adrenal cortex, the gonads have very different concentrations of key enzymes in their steroid pathways. Endocrine cells in both testes and ovaries lack the enzymes needed to produce aldosterone and cortisol. They possess high concentrations of enzymes in the androgen pathways leading to androstenedione, as in the adrenal cortex. In addition, the endocrine cells in the testes contain a high concentration of the enzyme that converts androstenedione to testosterone, which is therefore the major androgen secreted by the testes (Figure 10-6). The ovarian endocrine cells that synthesize the major female sex hormone, estradiol, have a high concentration of the enzyme (aromatase) required to go one step further—that is, to transform androgens to estradiol (Figure 10-6). Accordingly, estradiol, rather than androgens, is secreted by the ovaries.

Very small amounts of testosterone do leak out of ovarian endocrine cells, however, and very small amounts of estradiol are produced from testosterone in the testes. Moreover, following their secretion into the blood by the gonads and the adrenal cortex, steroid hormones may undergo further interconversion in either the blood or other organs. For example, testosterone is converted to estradiol in some of its target cells. Thus, the major male and female sex hormones—testosterone and estradiol, respectively—are not unique to males and females, although, of course, the relative concentrations of the hormones are quite different in the two sexes.

Finally, certain ovarian endocrine cells secrete another major steroid hormone, progesterone.

Essentials of Human Physiology

Essentials of Human Physiology

This ebook provides an introductory explanation of the workings of the human body, with an effort to draw connections between the body systems and explain their interdependencies. A framework for the book is homeostasis and how the body maintains balance within each system. This is intended as a first introduction to physiology for a college-level course.

Get My Free Ebook


Responses

  • nikola
    Are steroid hormones produced by the adrenal medulla?
    7 years ago
  • claudia
    Are t3 & t4 hormones adrenal or peptide?
    6 years ago
  • silvia
    What hormone enters the cell resulting in the synthesis of proteins?
    6 years ago
  • s
    Is T3 and T4 adrenal or peptide based?
    6 years ago
  • stig
    Are iodinecontaining hormones steroids?
    6 years ago
  • Klaus
    What are the function of amine in the body?
    5 years ago
  • MIKE
    How are amine hormones synthesized?
    4 years ago
  • Madihah
    Why these steps need preprohormone prohormone hormone?
    3 years ago
  • Tero
    Which cells secrete amine?
    2 years ago
  • Madoc T
    Which hormone is used by the body to synthesis hormones?
    1 year ago
  • reima
    How hormones are synthesied?
    1 year ago
  • Askalu
    How are hormones synthesised?
    12 months ago
  • bungo
    What is an amide hormone?
    6 months ago

Post a comment