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located at the base of the brain, to produce LH (luteinizing hormone) and FSH (follicle-stimulating hormone). The LH tells the testes to secrete the male hormone testosterone. Testosterone stimulates the sexual desires and develops

 Increased Decreased

Anti-insulin Antibodies

Antibodies against insulin hormone have been observed

in many conditions. These can be against endogenous or

exogenous insulin. It is found in Type 1 diabetes. These are

developed under insulin therapy. There are two types of

antibodies.

Against Endogenous Insulin

Antibodies against insulin, produced in the body (human

insulin).

Against Exogenous Insulin

Antibodies against insulin, taken by medication—insulin

injection (bovine, porcine and recombinant human

insulin).

Both types are present in the body. Detection of both

these types are important.

Glucagon is a small protein produced by alpha cells

within the islets that cause the level of blood glucose

to increase. Its release is controlled by blood levels of

glucose. As levels fall, glucagon release is increased

causing the release of stored glucose and the synthesis of

glucose until levels are increased and glucagon release is

then reduced via negative feedback. Glucagon opposes

the metabolic actions of insulin. This opposition plus the

negative feedback control of glucose levels maintain very

tight control on blood glucose levels.

TESTES

Testosterone is the principal hormone of the testes and

is synthesized from cholesterol by the Leydig cells. The

secretion of testosterone is under the control of LH from

the pituitary. The LH secretion is decreased by increased

levels of testosterone in the blood via negative feedback.

Testosterone develops and maintains the male secondary

sex characteristics, is anabolic and growth promoting

and participates in the formation of sperm. It also causes

aggressive behavior and increased libido. Body hair is

increased by androgens while scalp hair is decreased.

Like other steroids, testosterone enters cells and binds

to an intracellular receptor and then causes the production

of mRNA coding for proteins that manifest the changes

induced by testosterone. In some target tissues a form of

testosterone, DHT, is produced that has greater stability in

combination with the receptor and, therefore, produces a

longer lasting effect. The DHT is needed for the maturation

of the accessory glands and external genitalia, while testosterone is more important in the growth of muscle mass,

development of the internal genitalia and maintenance of

the male libido and sex drive.

Another hormone produced by the testes is the

polypeptide hormone, inhibin, produced by the Sertoli

cells. It inhibits FSH secretion by a direct action on the

pituitary.

Androgen Abnormalities

Androgen Excess

Males

¾ Children—precocious puberty

¾ Adults—infertility.

Females

¾ Hirsuitism and virilization

¾ Pseudohermaphroditism.

Androgen Deficiency

Males

¾ Improper growth—eunuchoid features

¾ Disappearance of body hair

¾ Muscular atrophy

¾ Infertility

¾ Testicular feminization.

Females

¾ Generally low in females.

OVARY

The ovaries produce the steroid hormones (estrogens and

progesterone) that cause the development of secondary

The Endocrine System 759

sexual characteristics and develop and maintain the

reproductive function in the female. Specifically, the

estrogens are secreted by the theca interna cells and the

granulosa cells of the ovarian follicle, the corpus luteum

and the placenta. The LH from the anterior pituitary binds

to receptors on theca interna or granulosa cells to cause the

production of estradiol from cholesterol or a downstream

precursor androstenedione that is passed from the thecal

cells to the granulosa cells. Progesterone is secreted mostly

by the corpus luteum and the placenta, but some are

made by the developing follicle. Negative feedback from

progesterone decreases LH secretion and large doses can

prevent ovulation.

Estradiol is the most potent and major secreted estrogen

although estrone and estriol can be found in circulation as

well. Like other steroid hormones, estrogens enter target

cells, combine with a nuclear receptor and cause the

production of mRNAs that, when translated into proteins,

modify cell function. Estrogens are metabolized by the

liver and secreted in bile where some are reabsorbed back

into the body. Metabolites of estradiol are excreted in the

urine.

Estrogens in the bloodstream inhibit the release of FSH

and LH, in some circumstances, via negative feedback. At

other times, as in the preovulatory LH surge, estrogens

increase the release of LH, via positive feedback. Estrogen

also increases the excitability of uterine smooth muscle,

myometrial sensitivity to oxytocin and increases the libido

in women by a direct action on hypothalamic neurons.

Estrogens lower plasma cholesterol, inhibit

atherogenesis (plaque formation in blood vessels), and

are protective against myocardial infarction as suggested

by the lower incidence of heart attacks and atherosclerosis

in premenopausal women.

Synthesis

Pregnant women: Placenta (mainly estriol—E3)

Nonpregnant women: Ovaries (mainly estradiol—E2).

Estrogen Abnormalities

Excess

¾ Menstrual irregularities

¾ Amenorrhea

¾ Hermaphroditism

¾ Hashimoto’s thyroiditis

¾ Addison’s disease

¾ Turner’s syndrome.

Deficiency

¾ Tumor of the ovary

¾ Hirsutism

¾ Infertility.

Progesterone has the principal targets of the uterus,

breasts and the brain. It promotes the development of

breast tissue, causes changes in the endometrial lining

during the luteal phase of the cycle, decreases the

excitability of myometrial cells and decreases uterine

sensitivity to oxytocin.

Progesterone Abnormalities

Excess

¾ Congenital adrenal hyperplasia

¾ Hirsutism

¾ Amenorrhea

¾ Infertility.

Deficiency

¾ Menstrual irregularities

¾ Hermaphroditism

¾ Corpus luteum deficiency.

PINEAL GLAND

The pineal gland can be found deep in the brain at the top

of the third ventricle where it is in close communication

with the cerebrospinal fluid. In the adult, the pineal

gland can often be seen in X-rays of the brain because

of the accumulation of radiopaque calcium phosphate

and carbonate into small granules called pineal sand. The

cells of the pineal gland secrete the hormone Melatonin

in a diurnal cycle (the amount changes throughout a 24

hours period) where the amount remains low during the

daylight hours but increases during the dark hours. This

diurnal variation is controlled by norepinephrine from

sympathetic nervous input that is regulated by the lightdark cycle in the environment.

Although some people use melatonin supplements to

treat insomnia, this effect has not been proven in scientific

trials. There have been reports of increased insomnia and

depression as well as other side effects associated with its

use.

HORMONES AND FERTILITY

Disturbance in the hormonal system is a major cause of

male and female fertility problems.

The brain plays a key role in regulating the hormones

that affect the development of sperm (spermatogenesis)

in males and regulation of menstrual cycle (ovulation)

in females. The process begins when the hypothalamus

(a part of the brain) emits a substance (gonadotropinreleasing hormone, or GnRH) that stimulates the pituitary

gland, located at the base of the brain. The pituitary

760 Concise Book of Medical Laboratory Technology: Methods and Interpretations gland then emits LH (luteinizing hormone) and FSH

(follicle-stimulating hormone). These stimulate testicular

development and sperm production in males and regulate

the menstrual cycle and release of ovum in females.

The LH and FSH also regulate the production of

steroid hormones responsible for male and female sexual

characteristics.

MALE FERTILITY

The Four Factors of Male Fertility

Pretesticular Function (Hormones)

Disturbances in the hormonal system cause about 10% of

male fertility problems.

Testicular Function

Testicular failure represents about 55% of male fertility

problems.

To respond to hormone stimulation properly, the

testicles, or testes, must be capable of producing sperm

(spermatogenesis).

Post-testicular Function

Tubal obstruction including vasectomy accounts for about

6% of male infertility.

The post-testicular system of ducts must be capable

of storing and delivering sperm. Sperm delivery system

problems include obstruction or interruption of the tubes

as a result of congenital malformation, disease, surgery, or

trauma.

Ejaculatory Disturbance, Impotence, and

Sexual Problems

Ejaculatory disturbances, impotence, and sexual problems

may prevent the delivery of sperm.

These disorders represent about 10% of male fertility

problems.

Problems associated with male infertility

The Male Hormone System

The Hypothalamus and Pituitary

Start the Action

Approximately every 90 minutes a specialized area in the

brain (hypothalamus) secretes GnRH (gonadotropinreleasing hormone). GnRH signals the pituitary gland,

located at the base of the brain, to produce LH (luteinizing

hormone) and FSH (follicle-stimulating hormone). The LH

tells the testes to secrete the male hormone testosterone.

Testosterone stimulates the sexual desires and develops

and maintains male secondary sex characteristics such

as hair growth and deep voice. Together, testosterone and

FSH stimulate the testes to produce sperm (spermatogenesis). The body’s ability to make and regulate these

hormones is vital for maintaining virility and sperm

production (Fig. 24.9).

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