STEROID

STEROIDS HORMONES

After a steroid hormone secretion by the endocrine glands, 95-98% will be in circulation or bound to a specific transport protein. 2-5% is freely diffuses into all cells. Once in the cell, can only produce steroid response in cells that have receptors for the hormone specific intracellular concerned. The bond between the hormone with specific receptors is key to the hormones in target tissues.

Thus:
• estrogen receptors found in the brain and reproductive cells specific targets for women such as uterus and breast.

• Hair follicles on the face, erectile tissue of the penis contains the androgen receptor

• glucocorticoid receptors are found in all cells because glucocorticoids needed to set the common functions such as metabolism and stress

All the faculties of the main group of sex steroids (androgens, progestins and estrogens) work through a series of similar work to produce a cellular response in the form of:

1. Transfer of steroid into the nucleus

2. Binding of intra-nuclear

3. Activates the receptor from an inactive form to an active

4. Binding of steroid-receptor complex to the DNA regulatory elements (desoksiribunukleic acid)

5. Transcription and synthesis of messenger ribonucleic acid (mRNA) in the new

6. MRNA translation by synthesizing new proteins in the cell

 Agonists and antagonists

The potential steroid hormone depends on:

1. The combination of hormone-receptor affinity or certain medications

2. Affinity hormone-receptor complex to the SRE-steroid receptor element

3. The efficiency of hormone-receptor complexes that are active in regulating gene transcription. Molecules with high affinity to the receptor and the hormone-receptor complex has a high affinity for the SRE will work as agonists of the parent compound.

Other molecules with high affinity to the receptor, but the bond between the hormone-receptor complex with the SRE less efficient antagonists will work with the parent compound. Tamoxifen is a compound with mixed agonist and antagonist properties.

Tamoxifen is an antiestrogen that works strongly to the estrogen receptor antagonist in breast and agonist on bone and uterus.

Clomiphene citrate can be used to ovulation induction. Clomiphene citrate interaction with estrogen receptors and the hypothalamic pituitary receptor binding will result in no further stimulation is accompanied by an efficient transcription of genes related to estrogen. The hypothalamus recognize this situation as a state hipoestrogen that GnRH pulse frequency increases. Production will pituitary FSH in stimulation and lead to increased levels of ovarian estrogen. Estrogen will work locally for recruitment of ovarian follicles in order to air ovulation. When clomiphene discontinued, the estrogen receptor in the hypothalamus is ready to bind again with SRE estrogen and respond accordingly. The hypothalamus can respond normally to high estrogen levels in the circulation and causing ovulation LH surge.

STEROIDS HORMONES IN CIRCULATION

Steroid hormone in the circulation is in the form of a bond with a specific protein. Hormones are bound by proteins do not penetrate the cell plasma membrane. Nearly 70% of testosterone and estradiol in the circulation bound to a β globulin known as SHBG-sex hormone - binding globulin. 30% are in a loose bond with albumin and a small portion (1-2%) in the free state and can enter into the cell. Synthesis of SHBG will increase in pregnancy, hiperestrogenemia and hyperthyroidism. Androgens, progestins, growth hormone and corticoids will lower SHBG synthesis. Changes in SHBG concentration will affect the amount of steroid in the circulation of free and not bound thereby affecting biological steroids work by changing the number of steroid-free entry into the cell.

METABOLISM STEROIDS

Unless progestins, androgens are obligatory precursors of the androgen steroid hormone that is made in all steroid-producing tissues, including the testes, ovaries and adrenal glands. The main androgen in the circulation in men is testosterone produced testes. Work androgen hormone produced directly by binding to androgen receptors or indirectly after conversion to DHT-dihydrotestosterone in the target tissue. Testosterone berkeja internal genital tract and the male fetus to stimulate muscle growth. In adult men, DHT acts locally to maintain the masculinization of the external genitalia and secondary sexual CIC as facial and pubic hair. Other types of androgens in men are: androstenedione, androstenediol, dehidroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEA-S).  

All types of androgens found in the circulation of women, except for androstenedione, the concentration of androgen in women less than men. Androstenedione in women acts as a prohormone and is converted in the target tissue to testosterone, estrone and estradiol. Estradiol (E2) is the major estrogen secreted by the ovaries. Estrone (E1) is also in the secretion by the ovaries in large quantities. Estriol (E3) is produced by the ovaries, but is produced from estradiol and estrone in peripheral tissues, the placenta of androgens; estimated is estriol less active metabolite of estrogen. The adrenal glands are the main source of sex steroids in men and women. Adrenal androgens play an important role in post-menopausal women. Progestin in circulation is at most progesterone. Progesterone is produced by the ovary, testis, placenta and adrenal glands. 17-hydroxyprogesterone from adrenal and ovarian cancers are the type most often found in the circulation

Excretion STEROIDS

Steroid excretion occurs via the urine and bile. Prior to elimination, occurs as sulfate conjugates or glukoronida. Several types of conjugates in forms such as DHEA-S in the active secretion. The hormones in these conjugated metabolites serve as precursors to active hormones in target tissues that have enzymes to perform hydrolysis of ester bonds involved in conjugation

Steroid hormones are divided into two groups, namely adrenokortikoid hormones and sex hormones.

A. Hormones Adrenokortikoid

Adenokortikoid hormone is a steroid hormone synthesized from cholesterol and is produced by glands adrenalis part of the cortex. Expenditure is influenced by hormones adrenokortiko tropin hormone (ACTH) from the anterior pituitary. This hormone is also called by the name adrenokortikosteroid, adrenocortical, corticosteroids or corticoids. Some relate to the physiological function of the cardiovascular system and blood, central nervous system, smooth muscle and stress.

Adrenokortikoid hormones are divided into two groups: mineralocorticoid and glucocorticoid hormones.

a. Hormones mineralkortikoid

This hormone is primarily used for the treatment of chronic Addison's disease, a disease caused by a malfunctioning gland adrenalis for any reason, eg gland tumors, resulting in the production of hormones decreases. Since Addison's disease is difficult to cure, then treatment can last a lifetime. This hormone can increase the intake of sodium ions and potassium spending ditubulus kidney.
Mechanism of action of mineralocorticoid hormones related to metabolism of electrolytes and water. This hormone is to maintain normal kidney function, namely by adjusting income and expenses natrim ion potassium ion. At the molecular level, these hormones interact to form complexes recovered resptor degan typical core embedded on the kidneys. Complex formation stimulates the synthesis of RNA and enzymes necessary for the active transport of Na ions, mineralocorticoid effect. Examples of mineralocorticoid hormones are: Aldosterone, Deoksikortikosteron and fludrocortisone.

b. Glucocorticoids Hormones

Glucocorticoid hormones have anti-inflammatory effects and is used to treat disorders of the collagen network, hematologic disorders (leukemia) and respiratory (asthma), for the treatment of rheumatism, arthritis pengobatn because of allergies, such as severe dermatological, gastrointestinal diseases and liver diseases. Effective for the treatment of glucocorticoid hormones schock Addison's disease, swollen brain, hypercalcemia, and myasthenia gravis. Glucocorticoid hormones can be dangerous if used improperly. Long-term use causes pretty severe side effects, such as hypokalemia, peptic ulcers, growth suppression, osteoporosis, round face, suppression of corticotropin secretion, atrophic skin, aggravate diabetes mellitus, mudsh infection, glaucoma, hypertension, menstrual disorders, and mental changes and behavior. Discontinuation of treatment suddenly cause acute adrenal insufficiency, and cause withdrawal symptoms, such as muscle becomes weak, muscle pain, fever, mental changes, muia, hypoglycemia, hypotension, dehydration and sometimes even cause death. Therefore, long-term treatment with glucocorticoids, drug discontinuation should be done gradually by reducing the dose.

Examples of drugs that belong to the hormones kortikosteroida is as follows:

 - Cortisone acetate

-Hydrocortisone

-Prednisone

-Prednisolone

-Methyl prednisolone

-Parametason

-Triamniolon

-Fluokortolon

-Betamethasone

-Dexamethasone