Physiology 5th Ed.

HORMONE SYNTHESIS

Hormones are categorized in one of three classes: peptides and proteins, steroids, or amines. Each class differs in its biosynthetic pathway: Peptide and protein hormones are synthesized from amino acids; steroid hormones are derivatives of cholesterol; and amine hormones are derivatives of tyrosine.

Peptide and Protein Hormone Synthesis

Most hormones are peptide or protein in nature. The biosynthetic pathways are familiar from biochemistry. The primary amino acid sequence of the peptide is dictated by a specific messenger ribonucleotide (mRNA), which has been transcribed from the gene for that hormone. The biosynthetic pathway for peptide hormones is summarized in Figure 9-2. The circled numbers in the figure correspond to the following steps:

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Figure 9–2 Steps involved in the synthesis of peptide hormones. See the text for an explanation of the circled numbers. DNA, Deoxyribonucleic acid; mRNA, messenger ribonucleic acid.

1.          In the nucleus, the gene for the hormone is transcribed into an mRNA. Generally, a single gene is responsible for directing the primary structure of each peptide hormone. (Because the genes for almost all peptide hormones have been cloned, recombinant DNA technology makes it possible to synthesize human peptide hormones.)

2.          The mRNA is transferred to the cytoplasm and translated on the ribosomes to the first protein product, a preprohormone. Translation of the mRNA begins with a signal peptide at the N terminus. Translation ceases, and the signal peptide attaches to receptors on the endoplasmic reticulum via “docking proteins.” Translation then continues on the endoplasmic reticulum until the entire peptide sequence is produced (i.e., the preprohormone).

3.          The signal peptide is removed in the endoplasmic reticulum, converting the preprohormone to a prohormone. The prohormone contains the complete hormone sequence plus other peptide sequences, which will be removed in a final step. Some of the “other” peptide sequences in the prohormone are necessary for proper folding of the hormone (e.g., formation of intramolecular linkages).

4.          The prohormone is transferred to the Golgi apparatus, where it is packaged in secretory vesicles. In the secretory vesicles, proteolytic enzymes cleave peptide sequences from the prohormone to produce the final hormone.Other functions of the Golgi apparatus include glycosylation and phosphorylation of the hormone.

5.          The final hormone is stored in secretory vesicles until the endocrine cell is stimulated. For example, parathyroid hormone (PTH) is synthesized and stored in vesicles in the chief cells of the parathyroid gland. The stimulus for secretion of PTH is low extracellular calcium (Ca2+) concentration. When sensors on the parathyroid gland detect a low extracellular Ca2+ concentration, the secretory vesicles are translocated to the cell membrane, where they extrude PTH into the blood by exocytosis. The other constituents of the secretory vesicles, including copeptides and cleavage enzymes, are extruded with PTH.

Steroid Hormone Synthesis

Steroid hormones are synthesized and secreted by the adrenal cortex, gonads, corpus luteum, and placenta. The steroid hormones are cortisol, aldosterone, estradiol and estriol, progesterone, testosterone, and 1,25-dihydroxycholecalciferol. All steroid hormones are derivatives of cholesterol, which is modified by removal or addition of side chains, hydroxylation, or aromatization of the steroid nucleus. The biosynthetic pathways for the adrenocortical hormones and for 1,25-dihydroxycholecalciferol are discussed in this chapter. The pathways for the sex steroid hormones are discussed in Chapter 10.

Amine Hormone Synthesis

The amine hormones are catecholamines (epinephrine, norepinephrine, and dopamine) and thyroid hormones. The amine hormones are derivatives of the amino acid tyrosine. The biosynthetic pathway for catecholamines is discussed in Chapter 1. The pathway for thyroid hormones is discussed in this chapter.