Biology of Disease

7.10 Reproductive Hormones

The male and female reproductive systems (Figure 7.34 (A)and(B)) produce

and secrete a number of sex hormones and are responsible for the maturation

of germ cells, the production of gametes and, in the female, the fertilization

of the ovum and its subsequent growth and development. The testes produce

male gametes or spermatozoa (‘sperms’) that mature and are stored in the

epididymis and vas deferens. Testes are composed of lobules with up to

three seminiferous tubules containing cells undergoing spermatogenesis.

These cells are supported and nourished by Sertoli cells. Spermatogenesis

involves meiosis and produces haploid sperm (Chapter 15) as outlined in

Figure 7.35. Each sperm has a head and a tail consisting of a midpiece and

flagellum. The midpiece contains mitochondria that provide energy for the

locomotory movements of the flagellum. The head contains a nucleus and

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Adrenaline (epinephrine) and noradrenaline (norepinephrine)

are catecholamine hormones secreted by the adrenal medulla.

They stimulate increases in heart, metabolic and breathing rates,

the depth of breathing and dilate blood vessels to muscles and

increase the metabolism of carbohydrate stores to prepare the

body for ‘fright, flight or fight’.

Pheochromocytomas are tumors of the adrenal medulla that

cause uncontrolled and irregular secretion of adrenaline and

noradrenaline. Such tumors are usually benign, that is they do

not metastasize (Chapter 17), and are rare causes of hypertension

(Chapter 14) accounting for some 0.5% of such cases.

Adrenaline and noradrenaline are metabolized to metadrenaline

and normetadrenaline respectively by catechol-O-methyl-

transferase (COMT). Metadrenaline and normetadrenaline are

converted to 4-hydroxy-3-methoxymandelic acid (HMMA), also

known as vanillylmandelic acid (VMA), by monoamine oxidase

(MAO). Metadrenaline and normetadrenaline and HMMA are all

excreted in the urine (Figure 7.33).

Patients affected by pheochromocytomas present with

headaches, pallor, tremors, increased heart rate and palpitations,

sweating and abdominal discomfort. Pheochromocytoma

leads to high levels of catecholamines in the plasma. However,

a diagnosis based on measurement of plasma levels is difficult,

as they are subject to variation by a number of factors including

posture. Screening tests include measuring and demonstrating

increased concentrations of urinary HMMA or metadrenaline

and normetadrenaline (Figure 7.33). The reference range for

urine HMMA is less than 35 Mmol per 24 h whereas those for

metadrenaline and normetadrenaline are less than 0.1 and less

than 0.57 Mmol per 24 h respectively. In cases where the results

are equivocal, the pentolinium test is conducted. Patients are

given 2.5 mg of pentolinium by intravenous injection. A blood

specimen is collected before and 15 min after the injection.

Pentolinium is a drug that inhibits release of catecholamines

in normal individuals but not in those suffering from

pheochromocytoma.

The treatment of pheochromocytoma involves surgical removal

of the tumor. However, it is necessary to block the action of

excess adrenaline and noradrenaline before any surgery by

administration of phenoxybenzamine. This is because during the

operation, the sudden release of large amounts of catecholamines

results in high blood pressure which, in turn, could cause a heart

attack or brain hemorrhage.

BOX 7.2 Pheochromocytoma

Figure 7.33 Metabolism of adrenaline and noradrenaline.

Adrenaline

DHMA

Noradrenaline

Metadrenaline

HMMA

Normetadrenaline

COMT COMT

COMT

MAO

MAO MAO

MAO

COMT catechol-O-methyltransferase

MAO monoamine oxidase

DHMA dihydroxymandelate

HMMA 4-hydroxy-3-methoxymandelate