HORMON

*FEMALE REPRODUCTIVE SYSTEM

PRIMARY FUNCTIONS OF THE FEMALE REPRODUCTIVE SYSTEM ARE:-[1] PRODUCTION OF FEMALE HORMONES.[2] FORMATION OF THE OVUM.[3] DEVELOPMENT OF THE reproduction organs.

*FEMALE REPRODUCTIVE ORGANS

*FEMALE EXTERNAL GENITALIA

*THE BREASTDEVELOPMENT OF THE BREAST DUCTS AND DEPOSITION OF FAT IN THE BREAST TISSUE IS STIMULATED BY ESTROGEN.DEVELOPMENT OF THE BREAST ALVEOLI IS STIMULATED BY PROGESTRONE.MILK PRODUCTION BY BREAST ALVEOLI IS STIMULATED BY PROLACTIN.MILK LET DOWN OR MILK - EJECTION IS STIMULATED BY OXYTOCIN.

*THE BREAST

*OOGENESIS

*THE OOCYTE

*THE FEMALE HORMONESHYPOTHALAMUS:- GONADOTROPIN RELEASING HORMONE [GnRH].PITUITARY:-LUTEINIZING HORMONE [LH] FOLLICLE STIMULATING HORMONE [FSH] PROLACTIN [PRL]OVARY:- DEVELOPING FOLLICLE:- ESTROGEN. CORPUS LUTEUM:- PROGESTRONE.

*THE FEMALE MENSTRUAL CYCLESARE CYCLIC CHANGES IN THE FEMALE REPRODUCTIVE SYSTEM THAT ARE CHARACTERIZED BY PERIODIC VAGINAL BLEEDING.THEY OCCUR AT THE SAME TIME AS:-OVARIAN CYCLEUTERINE CYCLE

*OVERIAN CYCLEFOLLICULAR PHASE:- THE DEVELOPMENT OF ONE PRIMARY FOLLICLE TO FORM A MATURE FOLLICLE. {ESTROGEN}OVULATION:- RUPTURE OF THE MATURE FOLLICLE TO RELEASE THE OVUM.LUTEAL PHASE:- FORMATION OF THE CORPUS LUTEUM FROM THE RUPTURED MATURE FOLLICLE. {PROGESTRONE} DEATH OF THE CORPUS LUTEUM WILL FORM A CORPUS ALBICANS.

*UTERINE CYCLEMENSTRUATION:- BREAKDOWN OF THE UTERINE ENDOMETRIUM AND VAGINAL BLEEDING DUE TO LOW ESTROGEN AND PROGESTRONE LEVELS.PROLIFERATIVE PHASE:- GROWTH OF THE UTERINE ENDOMETRIUM UNDER ESTROGEN STIMULATION.SECRETORY PHASE:- STIMULATION OF THE UTERINE GLANDS SECRETION BY PROGESTRONE.

*THE MENSTRUAL CYCLES

Hormonal Feedback and the Regulation of the Female Reproductive Function

Estrogen syntesisThe most potent naturally occurring estrogen in humans for both the Estrogen Receptor alpha- and beta-mediated actions is 17beta-estradiol, followed by estrone and estriolEach estrogen contains a phenolic A ring with a hydroxyl group at carbon 3 and a beta-OH or ketone in position 17 of ring DThe phenolic A ring is the principal structural feature responsible for selective, high-affinity binding to both receptorsSynthesis of estrogen begins from the synthesis of androstenedione from cholesterolAndrostenedione crosses the basal membrane into surrounding granulosa cells, where its converted to estrone or estradiol wither immediately or through testosteroneThe conversion is catalyzed by aromatase

Estrogens exert their effects by interaction with receptors that are members of the super family of nuclear receptorsThe two estrogen receptor (ER) genes are located on separate chromosomes: ESR1 encodes ER-alpha and ESR2 encodes ER-beta Both ERs are estrogen-dependent nuclear transcription factors that have different tissue distributions and transcriptional regulatory effects on target genesBoth ERs are ligand-activated transcription factors that increase or decrease the transcription of target genesAfter entering the cell by passive diffusion through the plasma membrane, the hormone binds to an ER in the nucleusIn the nucleus, the ER is present as an inactive monomer bound to heat-shock proteins, and upon binding estrogen, a change in ER confirmation dissociates the heat-shock proteins and causes receptor dimerization, which increases the affinity and the rate of receptor binding to DNA

Estrogen EffectEstrogens are also responsible for female secondary sex characteristics.Deposition of fat in the breasts and hips.Increased water retention.Affects calcium metabolism.Stimulates of breast development.Mediates female sexual behavior.

SERMSelective Estrogen Receptor Modulators (SERMs)Compounds with tissue-selective actionsThe goal of these drugs is to produce beneficial estrogenic actions in certain tissues (ex. Brain, bone, liver) during postmenopausal hormone therapyTamoxifen, Raloxifen, Toremifine

ProgesteronIn the reproductive tract, progesterone decreases estrogen-driven endometrial proliferation and leads to the development of a secretory endometriumThe abrupt decline in progesterone at the end of the cycle is the main determinant of the onset of menstruationProgesterone is very important for the maintenance of pregnancyIt suppresses menstruation and uterine contractility

Progesteron reseptorUnlike the ER receptor, which requires a phenolic ring for binding, the PR favors a non-phenolic ring structureThere is a single gene that encodes two isoforms of the progesterone receptor (PR): PR-A and PR-BSince the ligand-binding domains of the two PR isoforms are identical, there is no difference in ligand bindingHowever, the biological activities of PR-A and PR-B are distinct and depend on the target gene in questionPR-B mediates the stimulatory activities of progesteronePR-A strongly inhibits this action of PR-BUpon binding progesterone, the heat-shock proteins dissociate, and the receptors are phosphorylated and subsequently form dimers (homo- and hetero-) that bind with high selectivity to progesterone response elements located on target genes

Anti progesteron

Anti-progestin, first discovered in 1981, is mifepristone, used to terminate pregnancyIn the presence of progesterone, mifepristone acts as a competitive receptor antagonist for both progesterone receptorsWhen administered in the early stages of pregnancy, mifepristone causes decidual breakdown by blocking uterine progesterone receptors, which leads to detachment of the blastocyst, decreasing hCG production

Pubertydefined as transition period between sexually immature child to sexually mature, fertile adultinvolves growth and maturation of many tissuestiming has much individual variability

OVARIAN CHANGE DURING CHILHOODat birth, each ovary has ~500,000 folliclesno new follicles or eggs appear thereaftersome will partially develop during childhoodwill undergo atresia (insufficient LH and FSH)by puberty, each ovary has 83,000 follicles

Hormonal change at pubertyin young children, LH and FSH levels insufficient to initiate gonadal functionbetween 9-12 yrs., blood levels of LH, FSH increaseamplitude of pulses increases, especially during sleephigh levels of LH, FSH initiate gonadal development

GH secretion from pituitary also increasesTSH (thyroid stimulating hormone) secretion from pituitary increases in both sexes:increases metabolic ratepromotes tissue growth

Female Hormonal change surge of LH release initiates 1st ovarian cycleusually not sufficient to cause ovulation during 1st cyclebrain and endocrine systems mature soon thereafterestrogen levels in blood increase, due to growing follicles

estrogen induces secondary sex characteristics:growth of pelvisdeposit of subcutaneous fatgrowth of internal reprod. organs, external genitaliaandrogen release by adrenal glands increases > growth of pubic hair, lowering of voice, growth of bone, increased secretion from sebaceous glands

Hypotalamic maturation teoryActivation of reproductive system at puberty is due to maturation of hypothalamus. GnRH is driving force for pubertysupporting evidence:give immature monkey GnRH > will show ovulatory cycles with estrogen, LH surgestumors secreting GnRH can cause precocious puberty

Tyming of pubertytrend toward earlier puberty exists within Europe and USAexamination of lifestyle changes may give clues regarding mechanisms inducing onset

nutrionCritical body weight must be attained before activation of the reproductive system.earlier puberty due to improvement of nutrition, living conditions, healthcareevidence supporting hypothesis:obese girls go through early menarchemalnutrition is associated with delayed menarcheprimary amenorrhea common in lean female athletes

Precocious Puberty Precocious puberty is sexual maturation that begins before age 8 in a girl or before age 10 in a boy.In true precocious puberty, the sex glands (ovaries or testes) mature and a child's outward appearance becomes more adult. Pubic hair grows, and the child's body shape changes. In pseudoprecocious puberty, only the outward appearance becomes more adult, while the sex glands remain immature.True precocious puberty is two to five times more common in girls than in boys.

true precocious pubertyIt is due to increased production of pituitary gonadotrophins.

In pseudoprecocious pubertyIt is of peripheral origin. It is due to secretion of sex hormones; (estrogen or androgen) which is not dependent on pituitary gonadotrophins as in case of estrogenic or androgenic ovarian tumors.

Incomplete Precociuos PubertyIn this case only one pubertal change as breast development is present before the age of 8 years without the presence of any other pubertal changes and in absence of increased estrogen production. The other pubertal changes occur at the normal age.

Causes1. idiopathic: In most cases of precocious puberty (90%) , no cause is found. For some unknown reason the hypothalamus stimulates the pituitary gland to secrete its gonadotrophic hormones. There is normal menstruation and ovulation. Pregnancy can occur at young age

2.Organic lesions of the brain: The next common cause. Organic lesions affecting the midbrain, hypothalamus, pineal body, or pituitary gland may lead to premature release of pituitary gonadotrophins. Examples include traumatic brain injury, meningitis, encephalitis, brain abscess, brain tumor as glioma, craniopharyngioma, and hamartomas.

3. Adrenal causes: (a) Hyperplasia, adenoma, or carcinoma of suprarenal cortex. Congenital adrenal hyperplasia and Cushing syndrome lead to precocious puberty in the male direction, i.e. heterosexual precocious puberty; (b) Estrogen secreting adrenal tumor which is very rare.

4. Ovarian causes :(a) Estrogen producing tumors as granulosa and theca cell tumor; (b) Androgen producing tumors as androblastoma; (c) Choriocarcinoma because it secretes human chorionic gonadotrophin (HCG) which may stimulate the ovaries to secrete estrogen; (d) Dysgerminoma if it secretes HCG

5. Juvenile hypothyroidism: Lack of thyroxine leads to increased production of thyroid stimulating hormone and the secretion of pituitary gonadotrophins may also be increased.7. Drugs: latrogenic may follow oral or local administration of estrogen. A long course of estrogen cream used for treatment of vulvovaginitis of children may lead to breast development or withdrawal bleeding.

Symptom and DiagnosisIn both true precocious and pseudoprecocious puberty, a boy develops facial, under arm, and pubic hair. His penis lengthens, and his appearance becomes more masculine. A girl may start to have menstrual periods, especially if she has true precocious puberty, or she may develop breasts, pubic hair, and under arm hair. In boys and girls, body odor changes, and acne may appear.

Diagnostic tests include measuring blood hormone levels and taking x-rays of the hand and wrist to estimate bone maturity. Ultrasound examination of the pelvis and adrenal glands and computed tomography (CT) or magnetic resonance imaging (MRI) of the brain are performed to see whether tumors have developed in the adrenal glands, hypothalamus, or pituitary gland.

Delayed PubertySecondary Sexual Characters do not develop by the age of 14 y or no menstruation till age of 16y

Delayed PubertyIt is either :* Delayed onset: Breast bud does not appear till 13 years or menarche does not occur till 16 years . or* Delayed progreession : Menarche does not occur within 5 years after breast bud .

Etiology1 - Constitutional with have family history , short stature & normal fertility .2 - Hypergonadotropic hypogonadism3 - Hypogonadtropic hypogonadism = hypothalamic & pituitary causes of prymary amenorrhea, Anorexia nervosa .

4 - Normogonadtropic hypogonadism = end organ defects = uterine causes (Mullerian agenesis and testicular feminization syndrome), imperforate hymen (c/o = delayed menarche + normal other aspects of puberty).5 - General causes of amenorrhea (endocrinal or non-endocrinal especially malnutrition) if occurred before puberty &GH & steroid synthesis defects .

DiagnosisHistory :1 - Family history , nutritional history , any systemic diseases (e.g. history of endocrinal disturbance).2 - Clinical picture of space occupying lesion in the ovary , adrenal, pituitary & hypothalamus.3 - Periodic pain and have secondary sexual characteristics in imperforate hymen .

Examination :(A) Body measurement for causes of amenorrhea + or weight, short or tall stature , proportions (upper / lower segment ratio & arm span / height ratio).(B) Tanner staging of breast, pubic & axillary hair if present.(C) Clinical picture of Turner , Mullerian agenesis & imperforate hymen .(D) Neurological examination for,visual field & other cranial nerve lesions .

1 - FSH & LH assay important to differentiate level of the lesion & progesterone assay in 17 OH deficiency .2 - Chromosomal study if short stature or hypergonadotropic type .3 - Radiological bone age study & radiologic study for pituitary adenoma

Treatment* it treatable : Norethistrone acetate 5 mg twice daily for 21 d * Patient with Y chromosome cell line : Gonadectomy + hormone replacement therapy

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