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15.6.1: Human Hormones

The essence of multicellularity is the coordinated interaction of the various kinds of cells that make up the body. Cells communicate with each other by chemical signals. Three kinds of chemical signaling can be distinguished:

  • autocrine — the cell signals itself through a chemical that it synthesizes and then responds to. Autocrine signaling can occur solely within the cytoplasm of the cell or by a secreted chemical interacting with receptors on the surface of the same cell
  • paracrine — chemical signals that diffuse into the area and interact with receptors on nearby cells. Examples include the release of cytokines that cause an inflammatory response in the area and the release of neurotransmitters at synapses in the nervous system.
  • endocrine — the chemicals are secreted into the blood and carried by blood and tissue fluids to the cells they act upon.

This page will examine the properties of endocrine signaling.

Kinds of Hormones

There are two major classes of hormones:

  • proteins, peptides, and modified amino acids
  • steroids

Proteins, peptides and modified amino acids

These hydrophilic (and mostly large) hormone molecules bind to receptors on the surface of "target" cells; that is, cells able to respond to the presence of the hormone. These receptors are transmembrane proteins. Binding of the hormone to its receptor initiates a sequence of intracellular signals that may alter the behavior of the cell (such as by opening or closing membrane channels) or stimulate (or repress) gene expression in the nucleus by turning on (or off) the promoters and enhancers of the genes

Fig. !5.6.1.1 Protein hormone

This is the sequence of events:

  • The hormone binds to a site on the extracellular portion of the receptor.
    • The receptors are transmembrane proteins that pass through the plasma membrane 7 times, with their N-terminal exposed at the exterior of the cell and their C-terminal projecting into the cytoplasm.
  • Binding of the hormone to the receptor
    • activates a G protein associated with the cytoplasmic C-terminal
    • This initiates the production of a "second messenger". The most common of these are
      • cyclic AMP, (cAMP) which is produced by adenylyl cyclase from ATP
      • inositol 1,4,5-trisphosphate (IP3)
    • The second messenger, in turn, initiates a series of intracellular events (shown here as short arrows) such as
      • phosphorylation and activation of enzymes
      • release of Ca2+ into the cytosol from stores within the endoplasmic reticulum
    • In the case of cAMP, these enzymatic changes activate the transcription factor CREB (cAMP response element binding protein).
    • Once bound to its response element 5' TGACGTCA 3' in the promoters of genes that are able to respond to the hormone, activated CREB turns on gene transcription.
    • The cell begins to produce the appropriate gene products in response to the hormonal signal it had received at its surface.

Steroid Hormones

Fig. 15.6.1.2 Steroid receptors

Steroid hormones, being hydrophobic molecules, diffuse freely into all cells. However, their "target" cells contain cytoplasmic and/or nuclear proteins that serve as receptors of the hormone. The hormone binds to the receptor and the complex binds to hormone response elements — stretches of DNA within the promoters of genes responsive to the hormone. The hormone/receptor complex acts as a transcription factor turning target genes "on" (or "off").

Hormone Regulation

The levels of hormones circulating in the blood are tightly controlled by three homeostatic mechanisms:

  1. When one hormone stimulates the production of a second, the second suppresses the production of the first. Example: The follicle stimulating hormone (FSH) stimulates the release of estrogens from the ovarian follicle. A high level of estrogen, in turn, suppresses the further production of FSH.
  2. Antagonistic pairs of hormones. Example: Insulin causes the level of blood sugar (glucose) to drop when it has risen. Glucagon causes it to rise when it has fallen.
  3. Hormone secretion is increased (or decreased) by the same substance whose level is decreased (or increased) by the hormone. Example: a rising level of Ca2+ in the blood suppresses the production of the parathyroid hormone (PTH). A low level of Ca2+ stimulates it.

Hormone Transport

Although a few hormones circulate simply dissolved in the blood, most are carried in the blood bound to plasma proteins. For example, all the steroid hormones, being highly hydrophobic, are transported bound to plasma proteins.

Summary Table of Human Hormaones

Hormone Structure (1) Principal Source
 
Thyroid-stimulating hormone (TSH) protein (201) Anterior lobe of pituitary
Follicle-stimulating hormone (FSH) protein (204)
Luteinizing hormone (LH) protein (204)
Prolactin (PRL) protein (198)
Growth hormone (GH) protein (191)
Adrenocorticotropic hormone (ACTH) peptide (39)
Vasopressin peptide (9) Posterior lobe of pituitary
Oxytocin peptide (9)
Thyrotropin-releasing hormone (TRH) peptide (3) Hypothalamus
Gonadotropin-releasing hormone (GnRH) peptide (10)
Growth hormone-releasing hormone (GHRH) peptides (40, 44)
Corticotropin-releasing hormone (CRH) peptide (41)
Somatostatin peptides (14, 28)
Dopamine tyrosine derivative
Melatonin tryptophan derivative Pineal gland
Thyroxine (T4) tyrosine derivative Thyroid Gland
Calcitonin peptide (32)
Parathyroid hormone (PTH) protein (84) Parathyroid glands
FGF-23 (phosphatonin) protein (251) Bone
Osteocalcin peptide (49)
Erythropoietin (EPO) protein (166)
Glucocorticoids (e.g., cortisol) steroids Adrenal cortex
Mineralocorticoids (e.g., aldosterone) steroids
Androgens (e.g., testosterone) steroids
Adrenaline (epinephrine) tyrosine derivative Adrenal medulla
Noradrenaline (norepinephrine) tyrosine derivative
Estrogens (e.g., estradiol) steroid Ovarian follicle
Progesterone steroid Corpus luteum and placenta
Human chorionic gonadotropin (HCG) protein (237) Trophoblast and placenta
Androgens (e.g., testosterone) steroid Testes
Insulin protein (51) Pancreas (Islets of Langerhans)
Glucagon peptide (29)
Somatostatin peptides (14, 28)
Amylin peptide (37)
Erythropoietin (EPO) protein (166) Kidney
Calcitriol steroid derivative
Calciferol (vitamin D3) steroid derivative Skin
Atrial-natriuretic peptide (ANP) peptides (28, 32) Heart
Gastrin peptides (e.g., 14) Stomach and intestine
Secretin peptide (27)
Cholecystokinin (CCK) peptides (e.g., 8)
Fibroblast Growth Factor 19 (FGF19) protein (216)
Incretins peptides (e.g., 31, 42)
Somatostatin peptides (14, 28)
Neuropeptide Y peptide (36)
Ghrelin peptide (28)
PYY3-36 peptide (34)
Serotonin tryptophan derivative
Insulin-like growth factor-1 (IGF-1) protein (70) Liver
Angiotensinogen protein (485)
Thrombopoietin protein (332)
Hepcidin peptide (25)
Betatrophin protein (193)
Leptin protein (167) Fat cells (adipocytes)
Retinol Binding Protein 4 protein (~180)
Adiponectin protein (117)
Asprosin protein (140)

Note: Numbers within parentheses indicate the number of amino acids in the protein or peptide(s). 

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