BISC 307L 2nd Edition Lecture 22 Current Lecture Endocrine Events of Ovarian Menstrual Cycles The first and third row show changes in important hormones over the course of the ovarian cycle The average duration of the cycle is 28 days The 2nd row shows what the follicle looks like and the bottom is what the endometrium or innermost layer of the uterus looks like The 28 day cycle can be divided into two halves a follicular phase and a luteal phase The follicular phase is the first 14 days dominated by the events going on in the follicle in the ovary The luteal phase is dominated by the corpus luteum the remnants of the follicle after ovulation has occurred Day 1 is the onset of menstruation which is the first appearance of blood out of the vagina In the first few days of the cycle levels of estrogen are falling This estrogen has been coming from the corpus luteum and it is degenerating so estrogen levels are falling But then estrogen stops falling and begins to increase because the follicle is growing the theca cells are secreting testosterone which the granulosa cells convert to estradiol and that accounts for the rising levels There is also a positive feedback cycle involved because the estrogen itself stimulates the granulosa cells which are estrogen dependent greatly increasing the levels of estrogen As the follicle grows and secretes more estrogen estradiol rises In particular there are 6 10 follicles that move on to the second phase Through mechanisms that are not understood one follicle begins to grow more than the others It grows faster and faster and the others stop growing and regress In rare cases two of them will ovulate simultaneously and if they both get fertilized you get fraternal twins So the follicle increases its output of estrogen but ovulation occurs which injures the follicle so estradiol levels dip But that s just a temporary reduction because the remnant of the follicle that stays behind in the ovary will differentiate into the corpus luteum which pumps out estrogen and progesterone in increasingly higher levels So the estrogen levels purple trace in the 3rd row increase as the corpus luteum develops Progesterone is seen to be low in the first half because it is only secreted by the corpus luteum which develops in the second half of the cycle So in the third week we have high levels of progesterone and moderately high levels of estradiol But the corpus luteum has a fixed lifespan it will last only 10 days or so and then degenerate unless it gets continued gonadotropin support FSH and LH The levels of FSH and LH are pretty low however except for the spike in the very middle They reach their lowest levels in the second half of the cycle which is due to the high output of progesterone and estrogen in the second half that feeds back and inhibits the GnRH and therefore FSH and LH secretion These low levels of gonadotropins doom the corpus luteum to regression in 10 days However if fertilization occurs one of the extra embryonic membranes of the fetus called the chorion will secrete a chorionic gonadotropin that will support the corpus luteum and its estrogen and progesterone secretion throughout pregnancy The early appearance of chorionic gonadotropin is the basis for pregnancy tests and the most reliable early sign of pregnancy Inhibin levels are also shown on the third row inhibin is secreted by granulosa cells so its profile of secretion is about the same as that of estrogen This all began at menarche the beginning of reproductive cycling in girls and continues for 3040 years before becoming irregular and ceasing at menopause The traditional explanation of menopause is that the original supply of follicles at birth become depleted because no new ones are produced After menopause the levels of gonadosteroids are low because the follicles that secrete estrogen or progesterone are no longer available And because of the lack of negative feedback suppression levels of gonadotropins are high Because estrogen supports secondary sex characteristics in women like deposition of fat vaginal secretion during intercourse libido bone and muscle strength those things tend to wane in women during menopause Small dosages of estrogen given as hormone replacement therapy can reverse many of these changes and have been used extensively recently to fix these side effects However it was found that it raised chances of getting cancer so the number of women in developed countries who chose this route declined rapidly Pictured in the fourth row of the diagram is the endometrium of the uterus This tissue is sensitive to estrogen and progesterone and it will grow and differentiate in response to those hormones At the beginning levels of estrogen and progesterone are falling but they ve been high for a while at the end of the previous cycle so the endometrium has grown thick Within a short period of time the endometrium begins degenerating through necrosis they are murdered not apoptosis As the tissue expanded it became vascularized so these spirally blood vessels called spiral arteries grew with the wall and supplied blood to the thickened endometrium From the beginning of week 2 to the end of the cycle estrogen and progesterone are high preventing the synthesis of prostaglandins from the endometrium These prostaglandins if they were present would cause vasoconstriction In their absence blood flow is fine But when the levels of estrogen and progesterone fall at the end of the cycle due to the regression of the corpus luteum prostaglandin secretion is no longer suppressed The smooth muscle of the spiral arteries strongly constricts in response to these prostaglandins and the tissue dies a necrotic death because its blood supply is cut off These tissues become ischemic loss of blood supply and die After several days of this the tissue is pretty degenerated and no longer able to generate prostaglandins so prostaglandin levels go down as the tissue dies and vasoconstriction is relieved which results in more and more bleeding or menstruation So menstruation external bleeding is due to tissue being unable to produce any more prostaglandins And the point of this bleeding is to lift this degenerated tissue and flush it out of the uterine cavity Prostaglandins also activate contraction of the myometrium in different women so prostaglandin synthesis can cause painful contractions of the uterine smooth muscle causing menstrual cramps That is the menstrual phase the first 5 or so days The