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| GYNECOLOGIC OVERVIEW |
TOPICS |
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Gynecologic Overview
: A review of the genetic female's anatomy and physiology. |
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Vagina : The
passage leading from the vulva to the cervix of the uterus. |
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Uterus : The
hollow muscular organ where the fetus (baby) develops. |
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Breasts : The milk
producing mammary glands located over the pectoral muscles. |
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Hormones : Glands and
hormones responsible for health and development. |
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Hormones
Hormonal
communication systems augment the nervous communication systems within
the body. Hormones are chemical signaling molecules (peptides, proteins
or steroids) produced in one site of the body that then travel to
another site to have an effect. In this way one cell can effect other
distantly located cells. The endocrine system displays an elegant system
of checks and balances in the form of feedback loops to facilitate the
normal functioning of all bodily systems. Hormones may be made and have
an action locally or may be made in one endocrine gland and have an
effect at a distant site. Glands are functional units of hormone
secreting cells located in various regions of the body making up the
endocrine system. Each gland has specific functions that help to
maintain the normal internal environment and promote the survival of the
organism. Although there are some diffuse endocrine tissues, as in
the gastrointestinal epithelium, there are several major glands or
control centers within the endocrine system, including:
The
Pituitary Gland
The
pituitary gland, which lies is a small depression in the sphenoid bone
of the skull called the sella turcica, has often been termed the Master
Gland because many of the hormones it releases effect the release of
other hormones. However, the pituitary is really not the master. It is
controlled by a brain region called the hypothalamus via the release of
releasing factors into a special blood vessel network (hypothalamic-hypophyseal
portal system) that feeds the pituicytes. These releasing factors then
cause or inhibit the release of pituitary hormones which travel via the
circulatory system to the target organ. For example, as a woman's
menstrual cycle progresses toward ovulation, the hypothalamus releases
LHRH (luteinizing hormone releasing hormone) that travels via the
hypophyseal portal system to the pituitary where it stimulates the
production and release of LH (luteinizing hormone). LH then travels to
the ovaries where it causes ovulation and the subsequent development of
a progesterone secreting corpus luteum.
Anatomically
and functionally the pituitary can be divided into three portions:
1)
Anterior Pituitary (adenohypophysis)
Six peptide hormones are secreted by the adenohypophysis: Growth hormone
(somatotropin), corticotropin (ACTH), thyroid-stimulating hormone (TSH),
follicle-stimulating hormone (FSH), Luteinizing hormone (LH), and
prolactin. All except growth hormone and prolactin regulate the
activities of other glands. Somatotropin, PRL and ACTH are
polypeptide hormones and LH, FSH, and TSH are glycoproteins having very
similar structures.
- Growth
hormone: It has no specific target tissue. All cells
of the human body are affected by this hormone. It is very important in
the growing child but it remains essential to many bodily functions
throughout life. GH has effects on the growth of bone and cartilage,
protein metabolism, RNA formation, electrolyte balance, fat and glucose
metabolism.
- ACTH:
This trophic hormone stimulates the production and release of suprarenal
steroids. Normally the amount of circulating ACTH is controlled by the
levels of cortisol in the blood, individual biorhythms and stress.
- TSH:
This hormone stimulates the synthesis and secretion of thyroid
hormones. It is a glycoprotein hormone controlled by feedback from
thyroid hormones.
- FSH:
The target organs for FSH are the testes, in men, and the ovaries in
women. The hormone stimulates the germinal epithelium in the testes to
cause and facilitate the making of sperm. In women it stimulates the
growth and development of the follicle. It stimulates the production of
testosterone in men and estrogen and progesterone in women. Its release
from the pituitary is governed by a negative feedback mechanism
involving these steroids.
- LH:
The male target organ is the testes and the testosterone producing
interstitial cells of Leydig in particular. In women the target of LH is
the developing follicle within the ovary where it is necessary for
ovulation to occur and a corpus luteum to develop.
- Prolactin:
This hormone is involved in breast development and lactation. In concert
with estrogen, it prepares the mammary gland for lactation and then
causes the synthesis of milk. Secretion is regulated by a release
inhibiting factor and suckling may cause the release of prolactin from
the pituitary.
2)
Intermediate Lobe (pars intermedia)
In the adult human this lobe is diminished with poor vascular and neural
connections such that secretion is not facilitated. Cells in the pars
intermedia may secrete MSH (melanocyte stimulating hormone) which
stimulates the activity of melanocytes in the skin.
3)
Posterior Pituitary (neurohypophysis)
This portion of the pituitary is really an extension of the
hypothalamus. Neurons with their cell bodies in the hypothalamus and
their terminal protions in the neurohypophysis release two hormones.
Antidiuretic hormone (ADH) and oxytocin are stored there within the
terminal processes of neurons until the signal to release them is
received.
- ADH:
In the presence of ADH, the kidneys reabsorb more water from the forming
urine within the renal tubules. Without ADH the kidney tubules are
almost completely impermeable to water such that a very dilute urine is
excreted. ADH has a direct effect on vascular smooth muscle causing
vasoconstriction and an increase in blood pressure when present in large
doses. The hypothalamus has osmoreceptors that sense the concentration
of the blood. They are stimulated by a high blood osmolarity (increased
concentration) causing the release of ADH. The hormone then causes the
kidney tubules to reabsorb more water to return osmolarity to normal.
Volume receptors also play a role when they sense a low blood pressure.
Alcohol inhibits ADH secretion.
- Oxytocin:
A major role of this hormone is the stimulation of smooth muscle cells
in the pregnant uterus. When labor begins, stretching of the cervix and
vagina stimulates a reflex production and release of oxytocin. Oxytocin
then travels in the blood to the uterus where it causes more forceful
contraction of the smooth muscle. This hormone is also involved in
lactation. It causes milk ejection by acting on the smooth muscle
surrounding the milk producing cells. Again its production and release
is mediated by a neural reflex, the suckling reflex. Emotion, anxiety
and pain can inhibit oxytocin release.
Hypothalamus
Anterior
pituitary functions are controlled by the region of the brain called the
hypothalamus via the secretion of releasing and inhibiting
factors. Specialized neurons in the hypothalamus, controlled by feedback
and other communication methods release factors that cause the release
of hormones from the anterior pituitary. The pituitary trophic hormones
then control the release of other hormones from a target gland. With the
exception of prolactin, release promoting factors are more important to
the release of pituitary hormones. Somatostatin (inhibits GH
release), prolactin inhibiting factor (PIF), LH releasing factor (LHRF),
FSH releasing factor (FSHRF), prolactin releasing factor (PRF),
corticotropin releasing factor (CRF), thyrotropin releasing hormone
(TRH) are all hormones that control the release of anterior pituitary
hormones. The release of these factors is controlled by feedback from
the target organ hormone to maintain the proper hormonal balance.
Suprarenal
(Adrenal) Gland
The
suprarenal glands are located on top of each of the kidneys. The adrenal
cortex (outer portions) produce the corticosteroids: the
mineralcorticoids and the glucocorticoids which are steroid hormones.
The cortex also produces some male sex steroids. Cholesterol is the
starting place for the biosynthesis of all these steroid hormones.
The
adrenal medulla is actually an extension of the nervous system. The
adrenal medulla produces norepinephrine and epinepherine (adrenaline)
that are released in response to stress or a fright.
Mineralcorticoids
The major mineralcorticoid, which is secreted almost independently of
ACTH from the pituitary, is aldosterone. Aldosterone secretion is
controlled mostly by the levels of potassium and sodium in serum and a
blood pressure control system called the renin-angiotensin system. The
principle action of aldosterone is the retention of sodium. Where sodium
goes, so goes associated ions and water. Therefore, aldosterone
profoundly effects fluid balance by effecting intracellular and
extracellular fluid volume.
Aldosterone
has the opposite effect on serum levels of potassium as it is lost in
the urine in exchange for sodium in the renal tubules. Salivary and
sweat glands are also influenced by aldosterone to save sodium and the
intestine increases the absorption of sodium in response to aldosterone.
Aldosterone
levels increase and cause fluid retention in diseases such as congestive
heart failure and liver cirrhosis. Certain diuretics act by antagonizing
aldosterone. In contrast to most diuretics that cause potassium loss,
the aldosterone antagonists increase blood potassium and are sometimes
used for this effect.
Glucocorticoids
The major glucocorticoid is cortisol. Cortisol has important actions in
the control and metabolism of carbohydrates, lipids, and proteins and
assists in the metabolic reaction to stress, especially chronic stress.
It causes glucose to be liberated from the liver by increasing
glucose production from fatty acids (by-products of lipid breakdown) and
amino acids. Cortisol causes the tissues to take up less glucose from
the blood and mobilizes fat breakdown. The net effect is to increase
serum glucose concentrations which is protective for the brain in that
it cannot use any other fuel source than glucose. It also stimulates
protein breakdown for glucose formation in all tissues except the liver
where it stimulates protein synthesis.
At high
concentrations (greater than physiologic) glucocorticoids (such as
hydrocortisone or prednisone) are useful for the treatment of allergies
and inflammation. Each step of the inflammatory process is blocked by
glucocorticoids when given systemically (an IV injection or orally).
Topical application of glucocorticoids have anti-inflammatory effects
for the local area. The anti-inflammatory activity of glucocorticoids is
thought to be due primarily to the stabilization of cell membranes. The
immune response can also be suppressed by the use of glucocorticoids.
Eosinophils and lymphocytes decrease in the circulation affecting both
cellular and humoral immunity. The glucocorticoids are used for many
other conditions including asthma, renal diseases, rheumatic disorders
such as lupus and inflammatory bowel disease.
Thyroid
The thyroid is a large endocrine organ that functions mostly to control
metabolism. It is located in the neck between the trachea and larynx and
is bi-lobed with a connecting isthmus. The gland is composed of many
tiny follicles, that are in effect, each a separately functioning gland
with a single-layer epithelial lining. Each follicle accumulates a
storage form of the circulating thyroid hormones, thyroglobin.
Thyroglobin is a large protein molecule that contains multiple copies of
the amino acid tyrosine. The thyroid hormones are very simple
modifications of the amino acid tyrosine. Iodide is added to one or two
spots on the amino acid and then two of the modified tyrosines are
combined to form one of the two thyroid hormones, thyroxin (T4) or
triiodothyronine (T3). The thyroid hormones are then cut off the
thyroglobin as needed and released into the circulation. The thyroid
follicles accumulate iodine by extracting it from the blood and trapping
it within the lumen of the follicle. This ability to store hormone in a
large molecule is unique to the thyroid.
Both T4
and T3 enter cells and bind to an intracellular receptors whereby they
increase the metabolic capabilities of the cell. Mitochondria and
mitochondrial enzymes are increased thereby influencing cellular
metabolism. Thyroid hormones are necessary for normal growth and
development. They have metabolic effects on protein synthesis, lipid
metabolism and carbohydrate metabolism.
Also
produced by parafollicular cells within the thyroid is the polypeptide
hormone calcitonin. It functions in calcium maintenance to decrease the
levels of calcium in the blood. When serum calcium levels are excessive,
calcitonin is released. It inhibits bone resorption (by inhibiting
osteoclast activity), allows the loss of calcium in the urine and
therefore decreases calcium in the blood. It opposes the action of
parathyroid hormone and has been used clinically for the treatment of
osteoporosis.
Parathyroid
The four parathyroid glands lie on top of the thyroid gland in separate
nodes spread out to the four quadrants of the thyroid. Parathyroid
hormone is under direct feedback control of circulating levels of
calcium. If calcium levels fall, then parathyroid hormone is released.
As calcium levels rise, release of the hormone is reduced. Parathyroid
hormone acts on bones, the kidneys and the intestines to reabsorb
calcium.
Pancreas
The pancreas is a mixed exocrine and endocrine gland. The exocrine
portion makes many of the digestive enzymes necessary for
gastrointestinal function. The endocrine portion is comprised of
discrete islands of cells called the islets of Langerhans. Cells within
the islets produce two hormones that regulate the concentration of
glucose in the blood. Insulin is a polypeptide hormone produced by the
beta cells that reduces the level of circulating glucose. It is the only
hormone that reduces circulating glucose levels, is secreted in response
to high glucose levels and is subject to negative feedback control.
Insulin causes cells to take up glucose, stimulates the storage of
glucose, and inhibits the making of glucose.
Glucagon
is a small protein produced by alpha cells within the islets that causes
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
maintains very tight control on blood glucose levels.
Testes
Testosterone is the principle 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. 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. 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.
Ovary
The ovaries produce the steroid hormones (estrogens and progesterone)
that cause the development of secondary 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. 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 is 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 is reabsorbed back into the body.
Metabolites of estradiol are excreted in the urine.
Estrogens
in the blood stream 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.
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.
Cells of
the developing follicle also produce the polypeptide hormone inhibin
which inhibits FSH secretion by a direct action on the pituitary.
Pineal
The pineal gland can be found deep in the brain at the top of the third
ventricle where it is 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 hr 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 light-dark 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.
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