Review of Ovaries & Menstrual CycleReview:Ovarian functions: production of mature gametes (ova) by an oogenesis production of steroid hormones (steroidogenesis).

Endometrial cycle:

0 5 14 28

MENSES

17OH-P DAYSBASALBODY TEMP oC 37.0

38.0

PROGESTERONE

( )nmol/l

FSH

mU/l( )

LHmU/l( )

(

17-OESTRADIOL

pmol/l)

1. Menstrual phase – first day of menstruation beginning of cycle, lasts 4-5 days2. Proliferative phase – post-menstruation build up of endometrium, ~ 9 days. Growth of

follicles controlled by oestrogen of follicles. 2-3 fold increase in endometrial thickness, phase of repair and proliferation – epithelium repairs, gland increase number and length, spiral arteries lengthen.

Link with ovarian cycle: follicular phase – growth of follicle, when follicle has developed, the ovum is released ovulation (~ day 14)Hormonal control: pituitary – FSH and LH, ovary - 17 oestradiol

3. Secretory phase - ~13 daysProgesterone (and oestrogen)Formation of corpus luteum, glandular epithelium, thickening endometrium, spiral arteries.

The Ovarian Cycle:1. Follicular phase At the beginning of the menstrual cycle, ovarian

follicles begin to grow and develop Initially, each follicle consists of an outer layer of

thecal cells and an inner layer of granulosa cells which surround the ovum.

In the maturation process, the ovum increases in size and both groups of cells proliferate under hormonal influence.

The thecal cells form two distinct layers: an outer fibrous capsule (the theca externa) and an inner glandular and vascular layer (the theca interna).

The development and growth of follicles depends on the synthesis of specific hormone receptors and adequate levels of the relevant hormones; the adenohypophysial gonadotrophins luteinizing hormone (LH) and follicle-stimulating hormone (FSH).

Thecal cells LH receptors Granulosa cells FSH and

oestrogen receptors. The follicles which have reached this

stage of development with the necessary receptors when the gonadotrophins are present in the right quantities ripen. All other follicles will regress and be absorbed into the stroma atresia

Binding of LH to its thecal cell receptors stimulates these cells to synthesise androgens.

FSH binds to the granulosa cells which have a powerful aromatising enzyme (CYP450 aromatase) capable of converting thecal cell androgens to oestrogens.

Oestradiol released from the granulosa cells acts directly on these cells further proliferation and growth local positive feedback loop at the cellular level.

Insulin-like growth factor, IGF-I, is another hormone which is produced by the growing follicles and it probably plays an important role in growth and development processes.

As the plasma oestradiol levels rises during the mid-follicular phase, a selective negative feedback by the oestradiol in the FSH production occurs.

This effect, together with inhibin, (produced by the FSH-stimulated granulosa cells), results in a decrease in the plasma concentration of FSH

In the maintained basal presence of FSH, together with the increasing quantities of oestrogen, the outer layers of granulosa cells of the remaining (Graafian) follicle now synthesise receptors specific for LH.

This Graafian follicle is now capable of further maturation under the influence of its own oestrogens alone, and has no need for further FSH.

It enters the final maturation process which consists of the terminal growth of the follicle and the release of its ovum into the peritoneum by a process called ovulation. The stimulus for this event is a sudden surge in LH which is accompanied by a smaller surge in FSH (due to rise in oestrogen levels).

Just prior to ovulation, the granulosa cells begin to synthesise progestogens (mainly 17α-hydroxyprogesterone at this stage) instead of converting androgens to oestrogens.

These cells also gave reduced capacity to respond to oestrogens and FSH during this short, pre-ovulatory phase.

2. Luteal phase: Following ovulation rise in progesterone production by the outer granulosa cells small

increase in the basal body temperature (of the order of 0.3-0.6°C). This is a useful clinical indicator that ovulation has taken place.

LH surge causes conversion of the follicular remnants to a corpus luteum Some thecal cells become incorporated with the corpus luteum, composed principally of

hyperthyroid granulosa cells. These cells contain high concentrations of lipids and are rich in mitochondria, and their

transformation to luteal cells is associated with an increasing production of progesterone as well as oestradiol.

If pregnancy occurs, the corpus luteum persists and continues to secrete steroids until the foetoplacental unit can assume this function usually by the twelfth week.

If pregnancy does not occur the high plasma concentration of progesterone exerts a powerful negative feedback on the hypothalamo-hypophysial axis, in addition to any negative feedback by oestradiol and other luteal factors such as inhibin.

Consequently LH (and FSH) support is withdrawn, the corpus luteum degenerates (luteolysis), and ovarian steroid production decreases.

The luteolytic process in humans may also be influenced by the oestrogens produced by the luteal cells themselves.

Other luteolytic factors produced by the corpus luteum itself, such as oxytocin, may also be involved in luteolysis.

LCRS: Human Life Cycle - Review of Ovaries & Menstrual Cycle