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FISIOLOGIA DA REPRODUO FEMININA

CICLO HIPOTLAMOHIPOFISRIO

CICLO OVARIANO

CICLO HORMONAL

caso no ocorra a fecundao...

CICLO MENSTRUAL

preparo para possveis: FECUNDAO, IMPLANTAO, GRAVIDEZ E LACTAO

FASE LTEA

FASE FOLICULAR

Interaes dos hormnios ovarianos, hipotalmicos e adenohipofisrios durante o ciclo ovariano

http://sprojects.mmi.mcgill.ca/menstrualcycle/hypothalamicpituitaryaxis.html

padres de secreo dos hormnios esterides ovarianos e dos h. gonadotrficos

http://microanatomy.net/Reviews/Female%20reproductive%20review.pdf

FASE LTEA

FASE FOLICULAR

sugesto: a cada evento, associe-o s variaes dos hormnios gonadais e gonadotrficos demonstradas no grfico anterior

http://sprojects.mmi.mcgill.ca/menstrualcycle/hypothalamicpituitaryaxis.html

FASE FOLICULAR

lutelise

retroalimentao negativa

FSH

expresso da aromatase
estrgenos

expresso de receptores p/
FSH e LH folicular

http://sprojects.mmi.mcgill.ca/menstrualcycle/hypothalamicpituitaryaxis.html

FASE FOLICULAR

lutelise

retroalimentao negativa

FSH

expresso da aromatase
estrgenos

expresso de receptores p/
FSH e LH folicular

FSH

estrgenos

(6-7 dias do ciclo) (fase folicular inicial)


http://sprojects.mmi.mcgill.ca/menstrualcycle/hypothalamicpituitaryaxis.html

FASE FOLICULAR

FSH

estrgenos

(fase folicular inicial) Inibina B


FSH e LH ( 11 dias do ciclo) (fase folicular tardia)
Ao mesmo tempo, postulado que este aumento gradual de estradiol (por, no mnimo, 36 horas) exerce um efeito positivo, tanto no Hipotlamo quanto na hipfise, estimulando a sntese de GnRH, LH e FSH, importante para o futuro pico de secreo do GnRH, LH e, em menor proporo, do FSH (estoque).
http://sprojects.mmi.mcgill.ca/menstrualcycle/hypothalamicpituitaryaxis.html

FASE FOLICULAR

A dois dias da ovulao, ocorre:

estrgenos Progesterona
(amplifica o pico induzido pelos E2) receptores para LH (no folculo dominante) aps algumas horas:

GnRH LH
FSH (amadurecimento folicular)
Em mulheres, importante a prexposio do Hipotlamo e gonadotrfos ao E2 para a induo do aumento de receptores para a PG

http://sprojects.mmi.mcgill.ca/menstrualcycle/hypothalamicpituitaryaxis.html

FASE FOLICULAR

A dois dias da ovulao, ocorre:

estrgenos Progesterona
(amplifica o pico induzido pelos E2) receptores para LH (no folculo dominante) aps algumas horas:

GnRH LH
FSH (amadurecimento folicular) rompimento folicular

ovulao

http://sprojects.mmi.mcgill.ca/menstrualcycle/hypothalamicpituitaryaxis.html

O pico de LH necessrio para a ovulao. Sob a influncia do LH, o ocito primrio entra em seu estgio final da primeira diviso meitica e divide-se em ocito primrio e primeiro corpo de Barr. O pico de LH : -induz a liberao de enzimas proteolticas, que degradam as clulas na superfcie do folculo maduro -estimula a angiognese na parede folicular -estimula a secreo de prostaglandinas. Estes efeitos causam a ruptura e o esvazimento do contedo antral do folculo maduro.
Na ovulao, o ocito, a zona pelcida e a corona radiata so expelidos para a cavidade peritoneal. O ocito adere ao ovrio e contraes musculares e batimentos ciliares da trompa uterina fazem com que o ocito entre em contato com o epitlio da trompa e inicie sua migrao pelo oviduto.

FASE LTEA

FASE FOLICULAR

Aps a ovulao

luteinizao das cls. foliculares remanescentes por receptores para LH

Progesterona estrgenos

(at 6 dias aps ovulao) (corpo lteo)

http://sprojects.mmi.mcgill.ca/menstrualcycle/hypothalamicpituitaryaxis.html

FASE LTEA

FASE FOLICULAR

Progesterona estrgenos Inibina A

GnRH LH FSH

http://sprojects.mmi.mcgill.ca/menstrualcycle/hypothalamicpituitaryaxis.html

FASE LTEA

FASE FOLICULAR

LH atresia do corpo lteo


(corpo albicans)

Progesterona estrgenos Inibina A

http://sprojects.mmi.mcgill.ca/menstrualcycle/hypothalamicpituitaryaxis.html

FASE LTEA

FASE FOLICULAR

Progesterona e estrgenos

menstruao
Tambm ocorre a retirada da retroalimentao negativa sobre o Hipotlamo e hipfise e, consequentemente, a secreo de FSH deixa de ser inibida e comea a aumentar novamente, dando incio ao prximo ciclo menstrual.

http://sprojects.mmi.mcgill.ca/menstrualcycle/hypothalamicpituitaryaxis.html

http://microanatomy.net/Reviews/Female%20reproductive%20review.pdf

MAS COMO OCORREM ESSES PADRES DE SECREES DE GnRH, LH e de FSH?

http://mcb.berkeley.edu/courses/mcb135e/guest_lectures.htm

Estradiol e Progesterona modulam a secreo de GnRH, LH e FSH acionando diferentes mecanismos e em diferentes momentos no SNC, ora para reprimir,

ora para estimular a atividade dos nn. secretores de GnRH.

(Antunes et al., 2005)

Regulao das funes reprodutoras


Hormnio liberador de gonadotrofinas GnRH ( ou LHRH)

Caractersticas: Decapeptdeo Localizao dos neurnios hipotalmicos: em primata Hipotlamo Medial-Basal ARC (VM e EM)

em rato rea Pr-ptica (ncleo pr-ptico medial= gerador de pulso)

O Hipotlamo humano

ncleo ventromedial

ncleo arqueado

ncleo arqueado

eminncia mediana

sistema portahipofisrio

Hypothalamus, Tuberal Region. There are three important nuclei in the medial zone here; dorsomedial, the ventromedial and the arcuate nuclei. The arcuate nucleus exerts control over the release of pituitary hormones by releasing neurohormones (releasing and inhibiting factors) into the hypophyseal portal system. The ventromedial nucleus receives major input from the amygdala nuclei, and plays a role in mediating appetite and food intake (the nuclei in the lateral hypothalamus at this level also play a role in these behaviors). This frame shows a Nissl-stained section through the middle (tuberal region) of the hypothalamus of a nonhuman primate, at the point where the hypothalamus extends ventrally into the pituitary gland. The gland is seldom preserved during brain dissection, so all you see usually is the tuber cinereum (the floor of the hypothalamus) and the infundibulum (or infundibular stalk) from which the pituitary was suspended. http://www9.biostr.washington.edu/cgi-bin/DA/imageform

Influncias propostas para a regulao da secreo de GnRH pelos esterides ovarianos


E e PG 2: modulao transsinptica, influenciando outros ncleos intra e extrahipotalmicos

E e PG 1: efeito direto, no-genmico, de ao rpida

GnRH E e PG 3: alterao das relaes entre nn. GnRHrgicosclulas gliais

Potential modes and pathways of estrogen influence upon GnRH neurons. These include 1) direct nongenomic actions, 2) transsynaptic modulation, and 3) alterations in glial cell-GnRH relationships. Cells likely to express nuclear ERs are indicated by black nuclei. Herbison, 1998

Influncias propostas para a regulao da secreo de GnRH pelos esterides ovarianos na RATA

GnRH

Estradiol e/ou PG

Neuronal cell populations within the GnRH network implicated in transmitting estrogen input to GnRH neurons in the rat. This may be direct or indirect on the GnRH neuron and involve cell body or terminal levels of regulation. Note that the neurochemical identity of estrogen-receptive neurons within the GnRH network is not fully established. Neurons with black nuclei express nuclear ERs. An estrogen-receptive neuronal population in the AVPv is hypothesized to project to, and coordinate, neuronal activity within the arcuate nucleus. AVPv/preoptic = ncleo prptico medial de rato Herbison, 1998

O CICLO HORMONAL OVARIANO INDUZ OS CICLOS DOS EPITLIOS UTERINO E VAGINAL

Fase menstrual (5 dias)

Fase provulatria ( 9 dias)

ovulao

Fase psovulatria (14 dias)

Fase menstrual ( 5 dias)

Aes dos hormnios esterides ovarianos:


Metablicas:
Estrgenos (fase pr-ovulatria) produo pelo fgado de protenas plasmticas ligantes de vrios hormnios (Estradiol, Testosterona, Cortisol, HDL e VLDL e colesterol e LDL Progesterona (fase ps-ovulatria) temperatura basal corporal colesterol e HDL
Progesterona, Tiroxina e ligantes de ferro e cobre).

http://fisiologia.med.up.pt/slides%20TP/PDF/Fisiologia%20Reproducao.pdf

CARACTERSTICAS DO TERO

http://academic.pgcc.edu/~aimholtz/AandP/206_ONLINE/Repro/femalerepro1.html

Aes dos hormnios esterides ovarianos:


Extra-ovarianas:
TERO Eestrgenos (fase pr-ovulatria) Fase proliferativa uterina proliferao do endomtrio secreo cervical (secreo mucosa elstica)

Progesterona (fase ps-ovulatria) Fase secretora uterina proliferao mas as glndulas tornam-se tortuosas e secretoras (glicognio) proliferao e enovelamento de vasos sangneos secreo cervical (secreo mais flida e aqosa)

http://microanatomy.net/Reviews/Female%20reproductive%20review.pdf

http://microanatomy.net/Reviews/Female%20reproductive%20review.pdf

http://microanatomy.net/Reviews/Female%20reproductive%20review.pdf

Epitlio da trompa uterina

http://microanatomy.net/Reviews/Female%20reproductive%20review.pdf

Aes dos hormnios esterides ovarianos:


Regresso do corpo Lteo Estrgenos e Progesterona

Fase menstrual
Necrose focal no endomtrio que se desenvolveu; rompimento dos vasos sangneos com sangramento e descamao do endomtrio e vaso-espasmo (prostaglandinas PGF2)

Menstruao

Menstrual phase

http://microanatomy.net/Reviews/Female%20reproductive%20review.pdf

A RATA como modelo experimental para a observao da importncia dos hormnios ovarianos na fisiologia do tero

ovariectomia
ovrio

tero de rata bicorne ou bilobulado

desenhos do Prof. Dr. Norberto G. Cairasco, Fisiologia, FMRP, USP

Aps a ovariectomia, a diminuio dos estrgenos e da progesterona reduz o tamanho e peso uterino da rata. A terapia hormonal substitutiva adequada aumenta o peso uterino..

Aes dos hormnios esterides ovarianos:


Extra-ovarianas:
VAGINA Estrgenos (fase pr-ovulatria) proliferao e corneificao (ceratinizao) do epitlio (cls. esfoliativas, acidfilas e ncleos picnticos) secreo cervical (secreo mucosa elstica)

Progesterona (fase ps-ovulatria) cls. corneificadas presena de leuccitos polimorfonucleares.

Epitlio Vaginal

http://microanatomy.net/Reviews/Female%20reproductive%20review.pdf

Esfregao vaginal humano permite avaliar o status hormonal ovariano


Day 1-4 Day 5-9 Day 9-13 Day 13-14 Day 15-22 Day 23-28
Dr. Papanicolaou

Menstrual

Early Proliferative
mainly large and small basophilic (blue) stratum spinosum cells.

Mid Proliferative
stratum spinosum (blue) increase in size. Dark precipate outside cells are bacteria.

Late Proliferative, Ovulatory


mainly stratum corneum (red) which are large and flat, appear due to high estrogen levels.

Secretory

Late Secretory, (Ischemic) Premenstrual


stratum spinosum cells (blue) mainly with a few stratum corneum cells (red). Clustering of cells occurs at this stage and both leukocytes and bacteria are prevelant.

Both stratum corneum (red) and stratum spinosum (blue) epithelial cells will mostly blood. Leukocytes and bacteria may also be present. [coloured words are not links]

stratum spinosum cells (blue) which are folded or with curled edges, appear immediately after ovulation due to increase in progesterone. Leukocytes (small black cells) becoming more numerous.

http://embryology.med.unsw.edu.au/wwwhuman/MCycle/MCycle.htm http://www.papsociety.org/drpap.html

O ciclo estral de rata

Esfregao vaginal (HE) de rata nas fases do ciclo estral


Early dioestrus (metoestrus)

Late dioestrus

Pro-oestrus

Oestrus

http://137.222.110.150/calnet/Ovarian/page2.htm

MENOPAUSE Definitions

Menopause, or the climacteric, is the cessation of menses, diagnosed retrospectively after 12 months have passed without menstruation. In the Western world, menopause occurs at 51.4 years, on average, with a range of 40 to 58 years. The age at which menopause occurs is genetically determined, although cigarette smoking reduces the age of menopause by about two years.

http://www.arhp.org/healthcareproviders/cme/onlinecme/hormonetherapy/physiology.cfm http://www.menopause.org

SOB ADEQUADA ESTIMULAO DAS GONADOTROFINAS MENOPAUSA

(independente de gonadotrofinas)

Life history of ovarian follicles: endowment and maintenance, initial recruitment, maturation, atresia or cyclic recruitment, ovulation, and exhaustion. A fixed number of primordial follicles are endowed during early life, and most of them are maintained in a resting state. Growth of some of these dormant follicles is initiated before and throughout reproductive life (Initial recruitment). Follicles develop through primordial, primary, and secondary stages before acquiring an antral cavity. At the antral stage most follicles undergo atresia; however, under optimal gonadotropin stimulation that occurs after puberty, a few of them are rescued (Cyclic recruitment) to reach the preovulatory stage. Eventually, depletion of the pool of resting follicles leads to ovarian follicle exhaustion and senescence. Initial and Cyclic Recruitment of Ovarian Follicles. McGee & Hsueh, 2000 Endocrine Reviews

Neuroendocrine physiology of the early and late menopause. HALL, 2004 Hormonal integration of the reproductive system is dramatically affected by reproductive aging. The progressive loss of ovarian follicles Resumo da proposta with normal aging is accompanied by an initial decrease in inhibin B and a concomitant increase in follicle-stimulating hormone. Perda progressiva Subsequently, inhibin A and progesterone dos folculos ovarianos decrease, where as estradiol levels are (aumento da taxa de atresia >40 anos) maintained and often increase. In the late reproductive stage, cycles remain Inibina B regular whereas the early and late menopausal transition are characterized by irregular cycles c/ concomitante FSH and often dramatic swings in estradiol and gonadotropin levels. ou at dos estradiol Studies in younger and older postmenopausal (ciclos mais curtos) women suggest that there are age-related changes in the neuroendocrine axis that are independent Subsequentemente, of the changing ovarian hormonal milieu of the Inibina A e Progesterona menopausal transition but may contribute to the end of reproductive life. Hall JE, Endocrinol Metab Clin North Am. 2004 Dec;33(4):637-59.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15501638&dopt=Citation

MENOPAUSA Physiological Changes


In the past, researchers believed that menopause was caused solely by a lack of estrogen production by the ovary, resulting in higher levels of follicle-stimulating hormone (FSH) and cessation of menses. More recent evidence suggests that inhibin B, a glycoprotein synthesized by granulosa cells in the ovary, plays a major role in triggering the menopause transition. FSH normally stimulates inhibin B synthesis, which then suppresses FSH via a negative feedback loop. After about age 45, however, inhibin B levels fall, perhaps due to the decreased number of ovarian follicles, causing a rise in FSH. The increased FSH levels can stimulate increased estradiol release from the remaining follicles and can also prompt them to release the estradiol more rapidly, resulting in shorter cycles. About six to twelve months before menopause, the number of follicles is even lower, and higher FSH levels fail to increase estradiol production. At this point, the reduced estradiol levels can result in menopause-related symptoms, such as hot flashes and vaginal dryness. During perimenopause, estrogen production by the ovary is erratic, such that estradiol levels are unpredictable and can fluctuate between normal, high, and low. For this reason, measurement of FSH and estradiol is not helpful for diagnosis during perimenopause; symptoms are a better marker of perimenopausal status.
http://www.arhp.org/healthcareproviders/cme/onlinecme/hormonetherapy/physiology.cfm http://www.menopause.org

MENOPAUSA Physiological Changes

Table 1. Menopause-related Symptoms Vasomotor Headache Palpitations Night sweats Insomnia and sleep disturbances Hot flashes Genito-urinary Vaginal dryness Dyspareunia Vaginal itching or burning Urinary frequency, dysuria, nocturia Other systemic symptoms Fatigue Reduced sexual desire and arousal Anxiety, depression, irritability Cognitive difficulties Backache Stiffness

From menarche on, the number of primary ovarian follicles decreases, with especially marked reductions after age 40. The loss of primary ovarian follicles appears to be the key event that triggers perimenopause. Two key physiological changes are associated with menopause: the loss of primary ovarian follicles and the resulting decrease in serum and tissue estradiol levels. The primary estrogen in premenopausal women is 17 beta-estradiol, which is produced in the ovary from the aromatization of testosterone. Commercial estradiol products are often referred to as containing bioidentical estrogen for this reason. Other sites, such as muscle and adipose tissue, produce smaller amounts of estrogen through the metabolism of androgens. After menopause, these extragonadal sites become the primary source of estrogen, in the form of estrone and, to a lesser extent, estradiol. The physiological changes that eventually result in cessation of menses and the development of menopause-related symptoms begin long before menopause.

http://www.arhp.org/healthcareproviders/cme/onlinecme/hormonetherapy/physiology.cfm http://www.menopause.org

MENOPAUSA Physiological Changes


The risk of several medical conditions is increased with menopause. The incidence of osteoporosis increases substantially after menopause. Estrogen reduction leads to increased rates of bone resorption, although the rate of bone formation remains unchanged. By age 60, 25 percent of white and Asian women without estrogen therapy will develop spinal compression fractures. By age 80, 20 percent of white women without estrogen therapy develop hip fractures, and 15 percent of these women will die within six months from the fracture or its complications. It is not clear how menopausal changes increase the risk of osteoporosis, but it has been demonstrated that levels of serum calcium and phosphorus are increased, and the levels of parathyroid hormone and the active form of vitamin D are decreased . It is possible that estrogen therapy blocks the actions of parathyroid hormone on bone , thus reducing bone resorption. The risk of atherosclerotic disease, including coronary heart disease and stroke, increases with age. Before age 50, the gender ratio for myocardial infarction is 1:3, with men having the greater incidence of disease. However, after age 50, the rate of increase is greater in women than in men, so that by age 65, the ratio is 1:2, and by age 80 it is 1:1. Just as for men, cardiovascular disease is the leading cause of death of women. Investigators believe that total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglyceride levels increase after menopause, whereas high-density lipoprotein (HDL) cholesterol levels decline, promoting atherosclerosis.
http://www.arhp.org/healthcareproviders/cme/onlinecme/hormonetherapy/physiology.cfm http://www.menopause.org

CONTRACEPTIVOS Mecanismos de ao Os contraceptivos orais combinados funcionam atravs de trs principais mecanismos de ao. Aps serem ingeridos, so absorvidos no intestino e passam corrente sangnea. Atravs do sangue, circulam e chegam a hipfise e aos ovrios, impedindo a ovulao. Tambm fazem com que o muco do colo uterino (muco cervical) torne-se mais espesso, de forma a impedir a passagem dos espermatozides. O terceiro mecanismo de ao consiste em evitar que o endomtrio (revestimento interno do tero) esteja adequadamente preparado para a gravidez. Entendendo as plulas

Os contraceptivos orais da terceira gerao podem conter hormnios sintticos combinados (progestognios e estrognios) ou apenas progestognios. As variaes entre as plulas de primeira e terceira geraes ficam por conta da quantidade e do tipo de hormnio presentes em cada uma das marcas disponveis no mercado.
O etinil-estradiol o estrognio mais freqente dos contraceptivos orais combinados desde a primeira gerao das plulas. Foram somente as doses desse hormnio que variaram ao longo dos anos. Hoje, possvel encontrar contraceptivos no mercado que contm entre 0,1 a 0,015 miligrama de etinilestradiol, enquanto na primeira gerao as plulas chegavam a conter at 0,5 miligrama. J os progestognios variaram bastante, embora alguns deles, como o levonorgestrel, contidos na primeira gerao, ainda estejam presentes nas novas formulaes.

http://www.bebevirtual.com.br/website/saude_metodos_coc.asp

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