Endocrine signalling by hormones

Endocrine glands (or nerve endings for neurohormones) secrete hormones into the blood stream. They can be transported to almost any part of the body. For the hormones, receptors may thus be located in or on cells from distant tissues. Typical examples are: adrenaline which is secreted by the chromaffin cells of the adrenal medulla and which acts on a great number of tissues in the body and insulin which is secreted by the pancreatic P-cells and which acts on the liver and the adipose tissue. Since hormones are diluted in the bloodstream, they need to remain active at low

G Protein- Coupled Receptors: Molecular Pharmacology From Academic Concept to Pharmaceutical Research Georges Vauquelin and Bengt von Mentzer © 2007 John Wiley & Sons, Ltd. ISBN: 978-0-470-51647-8

Endocrine Mediators
Figure 1 Signalling by hormones, neurotransmitters and local chemical mediators Reprinted from Seeley et al., Anatomy and Physiology, 5th edn., © (2000), McGraw-Hill, with permission from the McGraw-Hill Companies.

concentrations (usually < 10~8M). According to their site of production, common vertebrate hormones can be divided into: pituitary, hypothalamic, thyroid, parathyroid, digestive, pancreatic, placental, gonadal, adrenal cortical, adrenal medullary, liver, kidney, cardiac and pineal hormones (Table 1, Figure 2).

The brain exerts a profound effect on the endocrine system via the pituitary gland (hypophysis), which hangs by a short stalk from the hypothalamus (i.e. part of the brain, Figure 3). It comprises two major portions:

• The posterior pituitary gland is an extension of the nerve tissue of the hypothalamus. It secretes antidiuretic hormone and oxytocin into the bloodstream.

• The anterior pituitary gland is a glandular tissue. Its hormones are secreted in response to releasing neurohormones secreted by the hypothalamus (these are carried by the bloodstream in the direction of the anterior pituitary gland). Involved (neuro)hormones are listed in Table 2. The pituitary hormones then stimulate their target cells in the body to make other low molecular weight hormones. The end products of these cascades feedback-inhibit hormone production at hypothalamic and/or pituitary levels (Figure 4).

Most peptide hormones are synthesised as preprohormones and must be processed further to produce the finished hormone. The synthesis of insulin in the pancreatic P-cells constitutes a typical example (Figure 5). The first peptide synthesised is 'preproinsulin'. The first 23 amino acids of this protein (i.e. the pre-piece) are very hydrophobic and are required for the penetration of the protein into the endoplasmic reticulum. The pre-piece is rapidly cleaved off in the endoplasmic reticulum, to form

Table 1 Examples of hormones involved in major physiological control of body functions (Zubay, 1993).

Hormone

Origin and structure

Major functions

ADRENAL CORTICAL HORMONES

GLUCOCORTICOIDS MINERALOCORTICOIDS

Steroids; cortisol and corticosterone Steroids; aldosterone

Diverse effects on inflammation and protein synthesis Maintenance of salt balance

ADRENAL MEDULLARY HORMONES

ADRENALINE (EPINEPHRINE)

NORADRENALINE (NOREPINEPHRINE)

Derived from tyrosine Derived from tyrosine

Glycogenolysis, lipid mobilization, smooth muscle contraction, cardiac function lipid mobilization, arteriole contraction

LIVER HORMONES

ANGIOTENSIN II

Peptide (eight amino acids)

Responsible for essential hypertension (also indirectly via release of aldosterone from adrenal cells)

KIDNEY HORMONES

CALCITROL [1,25-(OH)2-vitamin D3]

Derived from 7-dehydrocholesterol

Maintenance of calcium and phosphorous hoemostasis

PANCREATIC HORMONES

INSULIN

GLUCAGON

PANCREATIC POLYPEPTIDE

SOMATOSTATIN

Disulfide bonded dipeptide (21 and 30 amino acids)

Peptide (29 amino acids)

Peptide (36 amino acids)

Peptide (14 amino acids form)

Produced by P-cells of the pancreas, increases glucose uptake and utilization, increases lipogenesis, general anabolic effects Produced by a-cells of the pancreas, increases lipid mobilization and glycogenolysis to increase blood glucose levels Increases glycogenolysis, regulation of gastrointestinal activity Inhibition of glucagon and somatotropin release

Male Glands
Figure 2 Localization of major endocrine glands in the human (both male and female gonads, testis and ovaries are shown).

'proinsulin', a 9000 dalton protein. Proinsulin is then transported in small vescicles to the golgi apparatus. Here, it is packaged into secretory granules along with enzymes that are responsible for its conversion to insulin. This involves folding, disulfide bond formation and cleaving of the extra piece in the middle of the proinsulin chain to produce the 5600 dalton, two-chain insulin molecule. This conversion begins in the golgi complex, continues within the secretory granules and is nearly complete at the time of secretion (Figure 5B).

Several hormones are not secreted in their active (i.e. receptor binding and stimulating) form. They need to be further processed on their way to, or even within, their target cells. As an example, the peptide hormone angiotensin II is one of the most potent vasoconstrictors known and large quantities of angiotensin II appear in the bloodstream as a response to a drop in the arterial pressure. Its synthesis constitutes an example of the complex interplay between different extracellular factors (Figure 6). The kidneys will start to release renin in the bloodstream when the arterial pressure falls. Renin itself is an enzyme that splits the end off angiotensinogen (a plasma proteins that is secreted by the liver), to release a decapeptide, angiotensin I. Within a few seconds, two

Piolhos Higiene

Capillary loops j sî2lv \

I _r~jr*,___I Neurohormones trigger release of

' / Ij^s / ' - hormones by endocrine cells In ^V^JC / / anterior pitiutary

Capillary loops j sî2lv \

I _r~jr*,___I Neurohormones trigger release of

' / Ij^s / ' - hormones by endocrine cells In ^V^JC / / anterior pitiutary

Inferior hypophy seal vein carries hormones from anterior pituitary

Figure 3 Connection of the endocrine system to the brain.

Table 2 Hormones by which the brain controls major body functions (Zubay, 1993).

Hormone

Origin and structure

Major functions

HYPOTHALAMIC HORMONES

CORTICOTROPIN-RELEASING FACTOR

GONADOTROPIN-

RELEASING FACTOR PROLACTIN-RELEASING

FACTOR PROLACTIN-RELEASE INHIBITING FACTOR

GROWTH HORMONE-RELEASING FACTOR

Peptide (41 amino acids)

Peptide (10 amino acids)

This may be TRH

May be derived from GnRH precursor (56 amino acids) Protein (40 and 44 amino acids)

Acts on corticotrope to release ACTH and P-endorphin (lipotropin) Acts on gonadotrope to release

LH and FSH Acts on lactotrope to release prolactin Acts on lactotrope to inhibit prolactin release

Stimulates GH secretion

(continued)

(continued)

Table 2 (Continued)

Hormone

SOMATOSTATIN

THYROTROPIN-RELEASING FACTOR

OXYTOCIN

VASOPRESSIN

MELANOCYTE-STIMULATING HORMONE CORTICOTROPIN (ACTH)

LIPOTROPIN

THYROTROPIN (thyroid-stimulating hormone)

GROWTH HORMONE PROLACTIN

LUTEINIZING HORMONE

FOLLICLE-STIMULATING HORMONE

Origin and structure

Peptide (14 and 28 amino acids)

Peptide (three amino acids)

PITUITARY HORMONES

Peptide (nine amino acids)

Peptide (nine amino acids)

a peptide (13 amino acids) P peptide (18 amino acids)

Y peptide (12 amino acids) Polypeptide (39 amino acids)

P peptide (93 amino acids)

Y peptide (60 amino acids) a chain (96 amino acids) P chain (112 amino acids)

Protein (191 amino acids)

Protein (197 amino acids)

a chain (96 amino acids) P chain (121 amino acids)

a chain (96 amino acids) P chain (120 amino acids)

Major functions

Inhibits GH and TSH secretion

Stimulates TSH and prolactin secretion

Uterine contraction, causes milk ejection in lactating females, responds to suckling reflex and estradiol, lowers steroid synthesis in testes

Blood pressure regulation, increases H2O readsorption from distal tubules inkidney Pigmentation

Stimulates cells of adrenal gland to increase steroid synthesis and secretion Increases fatty acid release from adipocytes Acts on thyroid follicle cells to stimulate thyroid hormone synthesis General anabolic stimulant, increases release of insulinlike growth factor-I, cell growth and bone sulfation Stimulates differentiation of secretory cells of mammary gland and stimulates milk synthesis Increases ovarian progesterone synthesis, testosterone synthesis Ovarian follicle development and ovulation, increases estrogen production and spermatogenesis

Thyroid Hormone Synthesis
Figure 4 Control of hormone synthesis and secretion in the anterior pituitary. Example: follicle-stimulating hormone (FSH) is a protein acting on the gonads to stimulate the secretion of gonadal steroids.
Image Glucagon Preprohormone Structure
Figure 5 Structure (A) and synthesis (B) of insulin: preprohormones may be processed in cell to produce the hormone.
Synthesis Endorphin
Figure 6 Classical synthesis of angiotensin II: prohormones may be processed on their way to the target cells.

additional amino acids are split from angiotensin I, to form the octapeptide angiotensin II. This conversion occurs almost entirely in the small vessels of the lungs and it is catalyzed by an enzyme called 'angiotensin converting enzyme' (ACE) that is present in the walls of these vessels. Angiotensin II persists in the blood for a minute or so (since it is rapidly inactivated by a number of different blood and tissue enzymes) and it will produce vasoconstriction by binding to specific receptors. Angiotensin II (Ang II) is further metabolized to angiotensin III, angiotensin IV and Ang II (1-7) (Figure 6).

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  • Christen
    What is endocrine signalling?
    1 year ago

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