د. ساجدة فسلجة 20\2\2018
عدد الاوراق ( 11 ) م\2\موصل lec: 2REPRODUCTION AND HORMONAL FUNCTION IN FEMALE
Anatomy
The female reproductive organs include the ovaries , fallopian tubes & the uterus . during reproductive years ( 13-50 years ) about 450 follicle develop & expel their ova one each month .
Gonadotropic hormones & their effects on the ovaries
The ovarian changes during the female sexual cycle depend completely on the hormones FSH& LH secreted by the anterior pituitary .During fetal life , the ovaries are stimulated by hCG from the placenta but after birth the stimulation is lost .
The ovaries that are not stimulated by these hormones remain inactive that’s what occur in childhood when no FSH & LH secreted . at ages of 9-10 years the anterior pituitary begin to secrete FSH & LH which result in female sexual cycle between ages of 11-16 years . this period is called puberty & the first menstrual cycle is called menarche
OVARIAN CYCLE (MENSTRUAL CYCLE)
The normal reproductive years in female characterized by monthly changes in rate of secretion of female hormones , in the ovaries & sexual organs . the duration of menstrual cycle averages 28 days but may be as short as 20 days or as long as 45 days . as a result of this cycle :only one mature ovum is released from the ovaries each month .
the uterine endometrium is prepared for implantation of the fertilized ovum .
the absence of cyclic menstruation is called amenorrhea
the ovarian cycle consist of follicular phase & luteal phase .
Follicular phase
At childhood , the primordial follicle consist of ovum surrounded by single layer of granulose cells & believed to secrete an oocyte – maturation inhibiting factor that keep the ovum in primordial state .
After puberty when large quantities of FSH & LH secreted , the ovaries & the follicles begin to grow , so moderate enlargement of the ovum & additional layers of granulose cells formed , this is primary follicle , few days after beginning of menstruation , the concentration of FSH & LH increase several folds & the increase in FSH occur before LH by few days , these hormones cause growth of 6-12 primary follicles
each month .the initial effect is rapid proliferation of granulosa cells & formation of theca cells outside the granulose cells , theca interna cells secrete steroid hormones , while theca externa is highly vascular C .T capsule .
The granulosa cells secrete a follicular fluid that contain high concentration of estrogen , then antrum is formed , the granulose cells & theca cells proliferate rapidly to form vesicular follicle .
The estrogen secreted in the follicles cause the granulose cells to form increasing number of FSH receptors & making it more sensitive to FSH .as the vesicular follicle enlarges , after a week or more but before ovulation occur , one of the follicles begin to outgrow , while the remainder begin to involute & the process called atresia & the follicles are atretic follicles
the cause of atresia is unknown but it has been postulated that : the only follicle that becomes highly developed than the others secrete more estrogen this causes positive feedback effect that enhances granulose cell proliferation & enhances the number of FSH receptors on granulose cells thus increase the stimulatory effect of FSH on this follicle . however the secreted estrogen acts on the hypothalamus to decrease secretion of FSH & LH by pituitary thus decrease the stimulation to the less developed follicles .
Ovulation
large quantites of LH secreted by the anterior pituitary called the LH surge , LH is necessary for final follicular growth & ovulation & without this hormone ovulation not occur . two days before ovulation LH secretion increase 6-10 folds & peaks 16 hours before ovulation (LH surge ) . it is believed that the high level of estrogen at this time or the beginning of secretion of progesterone by the follicles causes appositive feedback effect on the hypothalamus & pituitary which leads to LH surge
FSH secretion also increase 2 – 3 folds & the two hormones cause rapid swelling of the follicle before ovulation .
The LH also has specific effect on granulosa & theca cells converting them to more progesterone secreting cells & less estrogen secretion so the rate of estrogen secretion decrease about one day before ovulation while small amount of progesterone secreted .
Large quantities of LH secreted cause rapid secretion of follicular steroid hormones that contain small amount of progesterone within few hours two events occur :
the theca externa release proteolytic enzymes cause dissolution of the capsular wall resulting in further swelling of entire follicle & degeneration of the stigma .
rapid growth of new blood vessels into the follicular wall & secretion of prostaglandins these cause transudation of plasma into the follicle & swelling of follicle . finally the swelling of the follicle & degeneration of the stigma cause follicle rupture & discharge of the ovum .
Indicators of ovulation
rise in body temperature occur in luteal phase (0.2-0.5 c ) due to thermogeneic effect of progesteronecervical mucus is slippery & copious , spinnbarket positive ( increase stretch ) .
abdominal pain , breast tenderness , mood changes ,
finding of a secretory pattern in a biopsy of endometrium indicates functioning corpus luteum .
Luteal phase of ovarian cycle
During first hours after expulsion of the ovum , the granulose & theca cells change into lutein cells & this change mainly dependent on LH & the process called lutenization & the total mass of the cells called corpus luteum the granulose cells of corpus luteum secrete large amount of progesterone & less estrogen . the theca cells secrete androstenedione & testosterone .
In normal female the corpus luteum grows to about 1-5 cm size reaching it 7-8 days after ovulation its life is extended to 12 days , then it involutes & loses its secretory function as well as its yellowish color & become corpus albicans . hCG maintain corpus luteum for 2-4 months of pregnancy .
Estrogen & to less extent progesterone secreted by the corpus luteum during luteal phase have negative feedback inhibition of FSH & LH secretion . in addition the lutein cells secrete inhibin this inhibit FSH secretion so as result the level of FSH & LH decrease & degeneration of the corpus lutum occur this called involution ( at 26th day of the cycle ) .
Endometrial cycle ( uterine cycle )
Uterine changes during the menstrual cycle includes : proliferative phase & secretary phase .Proliferative phase ( estrogen phase ) : at the beginning of each menstrual cycle , most of the endometrium is desquamated by menstruation , after menstruation only a thin layer of endometrial stroma remains . under the influence of estrogen secreted by the ovary , the stromal cells & the epithelial cells proliferate rapidly , the endometrial surface is re-epithelialized withen 4-7 days after the beginning of menstruation , then during the next week & a half that is before ovulation , the endometrium increase greatly in thickness due to increase number of stromal cells & progressive growth of endometrial glands & new blood vessels in the endometrium .
at the time of ovulation , the endometrium is about 3-4 mm thick . the endometrial glands especially in the cervical region secrete thin mucus .
Cervical changes : estrogen make cervical mucus thin & alkaline & help the transport of sperm , spinnbarkeit positive , fern like pattern when a thin layer spread over the slide .
Secretary phase ( progestational phase )
Occur after ovulation when large quantities of estrogen & progesterone secreted by corpus luteum . estrogen cause proliferation of endometrial cells while progesterone cause marked swelling & secretary development of endometrium . the glands increase in tortuosity , blood vessel become highly tortuous , at the peak of the secretory phase , about one week after ovulation , the endometrium is 5-6 mm thick , the cervical mucus become thick , tenacious & cellular & fail to form fern pattern .From the time the fertilized ovum enters the uterine cavity till implantation occur , the uterine secretion is called the uterine milk provide nutrition to the ovum .
Functions of estrogens
Effect on the uterus & external sex organs : at puberty estrogen cause increase in size of uterus , fallopian tubes & vagina , the external genitalia increase in size & deposition of fat in mons pubis , labia majora , &enlargement of labia minora . in addition estrogen the vaginal epithelium into stratified type which is resistant to infection . also estrogen causes marked proliferation of endometrium & development of endometrial glands .2. Effect on fallopian tubes : estrogen causes proliferation of glandular tissue & increase the number of ciliated epithelial cells that line the tubes which help to propel the fertilized ovum toward the uterus .
3. Effect on the breast : estrogen causes development of stromal tissues & growth of ductile system , also deposition of fat in the breast .
4. Effect on bones : estrogens cause increase osteoblastic activity & they cause early uniting of the epiphyses with the shaft of long bones that’s why the growth of female stops earlier than in male .
5. estrogen causes slight increase in total body protein .
6. estrogens increase ( B . M . R ) to about 1/3 less than testosterone do in male.7. estrogens cause deposition of fat in subcutaneous tissue in the buttocks & thighs .
8. esrtogens cause development of hair pubic region & axilla .
9. it cause the skin to become smooth & soft & more vascular & warm
10. it causes sodium & water retention by kidney tubules .
Functions of progesterone
it promote secretary changes in the uterine endometrium during the later half of female sexual cycle thus preparing the uterus for implantation of the ovum , also it decrease the frequency & intensity of uterine contractions .
it promote secretary changes in the mucosal lining of fallopian tubes which is necessary for nutrition of fertilized ovum .
3. it helps development of lobules & alveoli of the breast causing alveolar cells to become secretary , also causes the breast to swell .
4. it enhances sodium , chloride , water reabsorption by kidney tubules , competes with aldosterone on the same receptor protein that cause transport of sodium through the tubules & prevent aldosterone from binding .
Vaginal cycle
Under influence of estrogens , the vaginal epithelium become cornified & under influence of progesterone , a thick mucus is secreted & the epithelium proliferates & become infiltrated with leukocytes .Menstruation
Menstrual blood is mainly arterial & only 25% is venous . it is caused by the sudden decrease in estrogen & progesterone at the end of the monthly cycle , so less stimulation of endometrium by these hormones followed by involution of the endometrium to about 65% of its thickness during the 24 hours before menstruation , the blood vessele become vasospastic because of prostaglandins , this vasospasm & the loss of hormonal stimulation result in necrosis of endometrium , then gradually the necrotic outer layers of endometrium separate from the uterus until 48 hour after onset of menstruation . the menstrual blood is non-clotting because fibrinolysin is released with the necrotic endometrium , the duration of menstrual flow is 3-5 days but may be as short as one day or as long as 8 days average blood loss is 80 ml .Within 4-7 days after menstruation blood loss stop because the endometrium is re-epithelialized
Regulation of female monthly cycle
GnRH secreted from preoptic area & arcuate nucleus of the hypothalamus in pulses once every 1-3 hours & this result in pulsatile secretion of LH & to a lessor extent FSHThe pulsatile secretion of GnRH is important for its function because if secreted continuously , its effect on FSH & LH secretion is lost .
Estrogen in small amount has strong inhibition of FSH & LH secretion , also when progesterone is available , the inhibition of estrogen increase , while progesterone alone has little effect . in addition to the negative feedback effect of estrogen & progesterone , inhibin a hormone secreted by the granulosa cells of corpus luteum inhibit FSH secretion & to less extent LH secretion inhibition , it is believed that cause decrease in FSH &LH at the end of the monthly cycle .
Menopause
At ages of 40-50 years , menstrual cycle become less regular , ultimately it cease completely & this cessation is known as menopause . the phase of life beginning with menstrual irregularity & terminating in menopause is known as climacteric , it involves numerous physical & emotional changes as hot flushes , psychic sensation of dyspnea , irritability , fatiqability , & anexiety .
Menopause is caused primarily by ovarian failure , the ovaries lose their ability to respond to gonadotropins, only few primordial follicles stimulated by FSH & LH & the production of estrogen decrease . the hypothalamus & the anterior pituitary are functioning normally & secretes greater amounts of FSH & LH the main reason for that is the decrease plasma estrogen does not exert much negative feedback on gonadotropins secretion . a small amount of estrogen usually persist in plasma beyond the menopause , mainly from peripheral conversion of adrenal androgens to estrogen , but the level is inadequate to maintain estrogen dependent tissues .
The breasts & the genital organs gradually atrophy to a large degree . thining & dryness of the vaginal epithelium . marked decrease in bone mass & strength , osteoporosis may occur because of bone resorption & can result in bone fractures . the hot flushes so typical of menopause accompanied by dilation of the skin arteriols , a feeling of warmth & marked sweating , the incidence of coronary artery disease become similar in both sexes , a pattern that is due to the protective effects of estrogens . estrogen exerts beneficial actions on plasma cholesterol .
Female fertility
The ovum remains 24 hours capable of fertilization after it is expelled .the sperm remain fertile in female genital tract for 72 hours , so the fertile period in the female is 1-2 days before ovulation & up to one day after ovulation .Rhythem method of contraception
Coitus should be avoided for four days before calculated day of ovulation & 3 days afterward . if the periodity of the cycle is 28 days , ovulation occur on day 14 of the cycle , & if the periodicity of the cycle is 40 days , ovulation occur on 26th day .if the periodicity is 21 days , ovulation occur on the 7th day of the cycle .
Hormonal suppression of fertility "pills"
If estrogen & progesterone are given during the first half of the sexual cycle it prevent ovulation by preventing LH surge , among the synthetic estrogen is ethinylestradiol & mestranol , the synthetic progesterone is northindrone , norgestrel this medication is used from the 5th day of the cycle & for 21 days then stopped to allow menstruation . another type is called "minipill" , which contains only progesterone like substance this does not always prevent ovulation but it is effective because it affect the coposition of the cervical mucus , preventing passage of sperm through the cervix & they also inhibit the estrogen induced proliferation of the endometrium making it inhospitable for implantation .
PREGNANCY
Five weeks after implantation , the placenta become well established , the fetal heart begin to pump blood
In early pregnancy , the placental membrane is thick so its permeability is low , while late in pregnancy , the placental membrane is thin & more permeable . the main function of placenta is to provide for diffusion of food stuffs from the mothers blood into the fetouses blood & diffusion of excretory products from the fetus back to the mother .
Diffusion of oxygen through the placental membrane :
Dissolved oxygen in maternal sinuses transported to fetal blood by simple diffusion , po2 in mothers blood is 50mmHg while in fetal blood is 30mmHg . this figure shows the comparative oxygen dissociation curve of maternal Hb & fetal Hb demonstrating that the curve for fetal Hb is shifted to the left of that of maternal Hb this means that :at low po2 levels in fetal blood , the fetal Hb can carry 20-50% more oxygen than can maternal Hb .
the Hb concentration of fetal blood is about 50% greater than that of the mother .
the boher effect provides another factor that enhances the transport of oxygen by the fetal blood that is Hb can carry more oxygen at low pco2 than at high pco2 & by these three means the fetus is capable of receiving more than adequate oxygen through the placenta .
Diffusion of co2 through placental membrane
Pco2 of foetal blood is 2-3 mHg higher than that of maternal blood , this small pressure gradiant is sufficient to allow adequate diffusion of co2 .Diffusion of foodstuffs through the placental membrane
Glucose is transported by facilitated diffusion , fatty acids transported by diffusion . the excretory products as urea , uric acid & creatinine diffuse in maternal blood & excreted along with excretory products of the mother .
RESPONSE OF MOTHERS BODY TO PREGNANCY
Hormonal changesThroughout pregnancy , plasma concentration of estrogen remain high , estrogen secreted by syncytial trophoblast cells , the daily production increase to about 30 times the normal toward the end of pregnancy , the estrogen secreted by the placenta differs from these secreted by the ovaries .
Most of the secreted estrogen is esteriol which is weak estrogen .
The estrogens formed from dehydroepiandrosterone secreted by mothers & fetal adrenal glands .
RESPONSE OF MOTHERS BODY TO PREGNANCY
functions during pregnancy
Stimulates the growth of the uterine muscle mass which will eventually supply the contractile force needed to deliver the fetus
Enlargment of the breast , & of external genitalia
Relaxes the pelvic ligaments of the mother so these factors help the passage of the fetus through the birth canal .
Progesterone
secreted by the placenta , toward the end of pregnancy , the rate of secretion increase by 10 folds , its functions :Development of decidual cells in uterine endometrium
Decrease the contractility of pregnant uterus .
Increase secretion of uterus & fallopian tubes to provide nutrition for developing blastocyst .
It helps estrogen to prepare the mothers breast for lactation .
Human chorionic gonadotropin hcG
Secreted by syncytial trophoblast cells , the secretion of this hormone can be measured in blood by 8-9 days after ovulation , its detection in urine is used as a test of pregnancy , the secretion increase rapidly to reach a maximum about 10-12 weeks after ovulation , it decrease to lower level by 16-20 weeks & continue at this level to the remainder of pregnancy .Human chorionic gonadotropin hcG
FunctionsIt prevent the normal involution of corpus luteum at the end of the female monthly cycle .
Causes the corpus luteum to secrete estrogen & progesterone & this maintains the decidual nature of the endometrium , the corpus luteum involutes by 13-17 week of gestation .
hcG also stimulate testosterone secretion in the testis during pregnancy so male sex organs develop & testis descend in the scrotum .
Human chorionic somatomammotropin ( human placental lactogen)
Secreted by the placenta by the 5th week of pregancy & its secretion increase in direct proportion to the weight of placenta
Functions
Mobilizing fat for energy .
Stabilizing plasma glucose at relatively high levels (GH like effect )
Facilitating development of the breast .
Human chorionic somatomammotropin ( human placental lactogen)
Other hormonal factorsThe anterior pituitary enlarges by 50% & increase production of corticotropin , thyrotropin , prolactin while FSH &LH decrease .
Increase secretion of glucocorticoides & aldosterone .
Mothers thyroid increase by 50% & increase secretion of thyroxin .
Parathyroid increase especially in calcium deficient mothers .
Relaxin secreted by the corpus luteum , ovary & the placenta .
Increase secretion of vasopressin by posterior pituitary .
Other changes in pregnancy
The breast enlarges & develop mature glandular structure .Body weight increase by 12.5 kg , most of gain occur in the last two trimesters , due to fluid retaining hormones & increase desire for food .
Nutrition , a number of nutritional deficiences occur , as calcium , phosphate , iron , vitamins because these are not absorbed from her diet during the last month of pregnancy shortly before birth of baby , vitamin k is added to prevent hemorrhage particularly brain damage .
B.M.R increase by 15% during later half of pregnancy as a consequence of increase secretion of thyroxin , adrenocorticoids & sex hormones .
Changes in circulatory system
The cardiac output is increased by 30-40% above normal by the 27th week of pregnancy then fall to little above normal by the last 8 weeks of pregnancy .The maternal blood volume increase 30% above normal shortly before term this because of increase R.B.C by erythropoietin & increase fluid retension by aldosterone & estrogen.
Respiratory changes: the total amount of oxygen used by the mother is increased by 20% above normal shortly before delivery , the mothers minute ventilation increased by 50% because progesterone increase the sensitivity of respiratory center to co2 , respiratory rate is increased so pco2 decrease .
Renal changes the rate of urinary formation is increased because of increase load of excretory products , reabsorptive capacity for Na , Cl , H2O,is increase by 50% , G.F.R increased by 50% .
PARTURITION
A normal human pregnancy lasts about 40 weeks parturition means delivery of the infant followed by the placenta .Parturition is produced by strong rhythmical contractions of the myometrium .
What mechanisms control the events of parturition ?
The autonomic neurons to the uterus are of little importance in parturition since anesthetizing them does not interfere with delivery .
The smooth muscle cells of the myometrium have inherent rhythmicity & are capable of autonomus contraction , which are facilitated as the muscle is stretched by the growing fetus especially twins born 19 days earlier than single child .
The pregnant uterus near term & during labour secrets several prostaglandins that are profound stimulators of uterine smooth muscle contraction .
Oxytocin one of the hormones secreted by the posterior pituitary is potent uterine muscle stimulant . It is not only acts directly on uterine smooth muscle but also stimulate it to synthesize prostaglandins .
Oxytocin is released as a result of input to the hypothalamus from receptors in the uterus , particularly in the cervix . During pregnancy the number of oxytocin receptors in the uterus is increased mainly as a result of estrogen stimulation .
Throughout pregnancy progesterone exerts an essential powerful inhibitory effect upon uterine contraction by decreasing the sensitivity to estrogen , oxytocin & prostaglandins . Progesterone seem to play a major role in beginning parturition as the placenta ages the rate of progesterone secretion remains constant or decrease from the 7th month of pregnancy while estrogen secretion increase .
The fetuses pituitary secrete oxytocin that excites the uterus & its adrenal gland secrete large quantity of cortisol that stimulate the uterus , in addition the fetal membranes secrete prostaglandins in high concentration at time of labour , these increase the intensity of uterine contraction .
These factors once started , the uterine contraction exert a positive feedback effect upon themselves via both local facilitation of inherent uterine contractions & reflex stimulation of oxytocin secretion .
LACTATION
The anterior pituitary cells secrete PRL & this influenced by many hormones . They are inhibited by Dopamine which is secreted by the hypothalamus , they are stimulated by prolactin releasing factor which is also secreted by the hypothalamus & reaches the anterior pituitary by the portal vessels . Estrogen also acts on the anterior pituitary to stimulate PRL secretion .
Under the inhibitory influence of dopamine , PRL secretion is low before puberty , it then increase at puberty stimulated by the increased estrogen .
LACTATION
During pregnancy there is marked increase in PRL due to stimulation by estrogen . Also the placenta secrete human chorionic somatomammotropin which has lactogenic property . Despite the fact that PRL is elevated & the breast markedly enlarged , there is no milk secretion this is estrogen & progesterone in large concentration prevent milk production by inhibiting this particular action of PRL on the breast . So estrogen is antagonistic to prolactin’s ability to induce milk secretion .
Delivery removes this action & the inhibition of milk production . The drop in estrogen following parturition also causes basal PRL secretion to decrease from its peak late – pregnancy levels & after several months to return toward pregnancy levels although the mother continue to nurse .
There is large secretary bursts of PRL during each nursing . The episodic pulses of PRL are signals to the breasts for maintenance of milk production . The reflexes mediating the PRL bursts are initiated by afferent input to the hypothalamus from nipple receptors stimulated by suckling . This inputs the hypothalamic neurons that release dopamine & stimulate the neurons that secrete PRF .
The secretion of milk need the action of GH , cortisol , & parathyroid hormone , these hormones are necessary to provide A.A , F.A , glucose & calcium to the milk .
Ejection of milk
When baby suckles the breast , nerve signals transmitted to the spinal cord & then to the hypothalamus cause oxytocin secretion which result in contraction of myoepithelial cells surrounding the alveoli & ejection of milk . Generalized sympathetic stimulation inhibit oxytocin secretion & milk ejection .
Suppersion of sexual cycle during nursing
In about half of nursing mothers , ovarian cycle & ovulation stops until few weeks after cessation of lactation & is thought that the same signal from the breast to the hypothalamus that increase PRL secretion inhibit GnRH secretion & this in turn inhibit FSH & LH after several months of lactation in half of lactating mothers , the pituitary begin again to secrete FSH & LH & ovarian cycle return .