Menstrual Cycle

Key Facts

Ovarian and Endometrial cycles combine to form the menstrual cycle

Controlled by hypothalamus, pituitaryt ovarian axis

Ovarian Cycle: Refers to changes that occur in the ovary each month during menstrual cycle

Endometrial cycle: Cyclic growth and shedding of endometrium each month in respnse to estrogen and progesterone

Important hormones

GnRH, FSH, LH, Estrogen, progesterone

GnRH -> Stimulates LH and FSH -> Stimulates Estrogen adn progesterone -> Stimulate growth and maturation of ovarian follicles and preparation of endometrial lining

Glands

Hypothalamus

Importatn for reproduction

Contains nuclei with medial preoptic (GnRH), Arcuate (GnRH, GHRH, dopamine)

Pituitary Gland

Leader of endocrine system

Anterior pituitary gland: mostly cellular, very vascular, secretes FSH,LH,PRL, GH, TSH, ACTH, controls ovaraian function

Posterior: Secretes vaspressin and oxytocin

Hormones

GnRH

GnRH is secreted in pulses

As intervals decrease the GnRH favours the luteal phase

Constant release will suppress gonadotropin hormones

Steroid hormones

Estrogen and progesterone decreases GnRH release

FSH and LH decreases GnRH release

GnRH decreases its own release

Neutrotransmitters

Dopamine, acetylcholine, noradrenaline, serotonin, inhibin

FSH

Components

Composed of alpha and beta subunits

Actions

Stimulates growth of ovarian follicles

Stimulates aromatase activity and production of estrogen

Stimulates formation of LH receptors

Leads to ovulation with LH

Levels

Begins to increase at end of previous menstrual cycle

Decline in FSH levels at mid-follicular phase via negative feedback (estrogen and inhibin)

Small increase in progesterone concentrations generates FSH level surge, and occurs with LH surge

LH

Structure

Water soluble containing alpha and beta subunits

Action

Induces androgen production

Sitmulates proliferation, differentiation and secretory activity

Leads to oocytes to complete first meiotic division, rupture of mature follicle/ovulation, luteinization of theca and granuolsa cells

Receptors

On surface of theca cells

Level

: Peaks on day 13 of 28 menstural cyucle

Inhibin

Characteristics

Peptide hormone secreted by granulosa cells

FSH stimulates production of inhibit by grnaulosa cells, and works with estradiol to inhibit FSH release

All inhibin levels decline with loss of luteal functiona nd remain low

Estradiol

Characteristics

Sex steroid hormone derived from cholesterol and produced by granulosa cells

In menstrual cycle

Drop at ovulation, rise during luteal phase, and drop to menstrual levels at lureal phase unless there ia pregnancy

Physiological Effects

Rise in estrogen levels -> Growth spurt, maturation of internal and external genitalia

acts AS trophic hormones for tissues of reproductive tract

LH surge

Thickens endometrium during follciular phase

Progesterone

Characteristics

Sex steroid derived from cholesterol

Produced by ovaries and placenta, store in adipose tissue

In menstrual cycle

Low during preovulatory phase, rise after ovulation, and are elevated in luteal phase

In pregnancy, hCG is released to maintain corpus luteum to maintian lvevels of progesterone

Physiological Effects

Converts endometrium to its secretory phase

Antagonized mitotic effect of estrogen

Makes vaginal epitheliuma nd mucus thick and impenetrable to sperm

Decreases maternal immune response

Decreases contractiltiy of uterine smooth muscle

Inhibits lactation during pregnancy

Androstenedione

Sex steroid derived from cholesterol, produced by testicles, adrenals and ovarain cortex

Precursor for production of estrone

Released by ovarain theca cells, and is used as a precursor for production of estradol

Physiological Effects

Promotes protein synthesisi

Effects are anabolic and virilizing (testeosterone)

Cause enlargemenmt fo sebacious glands and acne, increased libido, pubic hair and axillary hair growth

Menstrual Cycle

Oogenesis

Ovarian differentiation begins at 6-8 weeks gestation

Follicles

Follicular growth

85 days for rimary follcile to progress to point of ovulation

Independent of gonadotropins to produce cohort of follicles that will develop in response to FSH stimulation

Number of mature follicles that matrue is dependent on amont of FSH and sensitivty to gonadotropins

Ovarian Cycle

If implantation occurs, luteum produces hormones to maintain pregnancy

Corpus luteum makes hormones to regulate endometrial cycle

Follicular Phase

Goal: Develop viable follicle

Early events initiation: Decrease in estrogen/progesterone at end of previous cycle, increase in FSH levels

Follicle Stages

Priamry follicle: Growth and differentation of primordial follicle -> primary follicle

Gonadotropin independent, stimulus unknown, major time of oocyte growth

Antral Follicle

Gonadotropin dependent

Granulosa cells proliferate and a fluid filled cavity called antrum develops

Single follicle destined to become domiannt grows at faster rate (tertiary follicle)

Deficiency in FSH and FSH receptors in other follicle inhibits estradiol production (accumulation of androstenediones -> atresia of follicles)

Graafin Follicle

Final stage of focllucular developemnt

Granulosa cells divided into 2 groups

Mural granulosa cells: Thin layer along periphery of follicle

Cumulus Oophorus: surrounds oocyte; inner most cells called corona radiata

Oocyte undergoes cytoplastmic and nuclear maturation to prepare oocytesfor embyogeneiss

Ovulatory Phase

Prior to ovulation: Estrogen increases rapidly, generates LH surge to complete meiosis 1 in oocytes

Ovulation Mechanism

Pressure thinning of tissue on the surface opf the follicle by rapid increase in antral fluid

Pg stimulate contraction of myofibrils

LH surge triggers activation of proteolytic enzymes (plasmin and collagenase)

At time of Ovulation

Follicle rupture to release oocyte, granulosa and theca cells remain in ovary

Luteal Phase

Corpus luteum forms under effect of LH

Granulosa and tehca cells proliferate and undergo hyperthrophy to form granulosa-lutein cells

Cl produces high levels of progesterone, and moderate levels of estradiol and inhiibin

Wihtout pregnancy, corpus luteum regresses

Endometrial Cycle

About Endometrium

Innermost glandular layer which is a lining of uterus

During menstrual cycle, endometrium grows thick, blood vessel rich layer

2 Layers

Basal Layer

Function layer

Stratum compaftum: Supreficial of gland necks and dense stroma

Stratum spongiosum: Glands and large amounts of loosely organized stroma nad interstitial tisue

Proliferates in response to estrogen, rebuilds after menstruation

Not shed and responisble for development of functional layer

Menstural Phase

Dayu 1-4 of a menstrual cycle

Periodic desquamation of endometrium

Leukocytes/Cytokines invovled in inflammatiory reaction

Plasmin and matrix: tissue breatdown

PG; Constric spiral arterioles leading to ischemia and desquamation

Proliferative Phase

Day 4-14 of mentsural cycle

Glandular and stromal cells of functional layer proliferate rapidly

Glands become more tortuous and cells lining glandular lumen undergo pseudostratification

Tubular glands with columnar cells and dense stroma proliferate

Secretory Phase

Day 15-28 of cycle

Begins at ovulationa and correlates with ovarina luteal phhase

Glands are coiled, more edematous

Secretions rich in glycogen and glycoprotein

If pregnancy does not occur, corpus luteum rdegenerates and lack of progesteon causes spiral arteries to constrict and endometrial tissue to become ischemic