Menstrual Cycle & its Hormonal

Regulation

by
Sk Sariful Islam
(Assistant Professor)
Hooghly Mohsin College
P.G. Department of Zoology

B.Sc. Semester-VI (Honours)

Date: 29th April, 2024
• Unlike the continuous sperm production and essentially constant
testosterone secretion characteristic of the male, the release of
ova is intermittent, and secretion of female sex hormones
displays wide cyclic swings.
• The female hormonal system consists of mainly three hormones:
GnRH from hypothalamus, FSH and LH from anterior pituitary;
and estrogen and progesterone from the ovaries.
• The normal reproductive years of the female are characterized
by monthly rhythmical changes in the rates of secretion of the
female hormones and corresponding physical changes in the
ovaries and other sexual organs. This rhythmical pattern is called
the female monthly sexual cycle or menstrual cycle.
• The duration of the cycle averages 28 days but this varies among
women and among cycles in any particular woman.
• It may be as short as 20 days or as long as 45 days in some
women, although abnormal cycle length is frequently associated
with decreased fertility.
• There are two significant results of the menstrual
cycle. First, only a single ovum is normally released
from the ovaries each month, so that normally only
single fetus will begin to grow at a time.
• After the onset of puberty, the ovary constantly
alternates between the two phases: the follicular
phase, which is dominated by the presence of
maturing follicles and the luteal phase, which is
characterized by the presence of corpus luteum.
• The follicle operates in the first half of the cycle to
produce a mature egg ready for ovulation at midcycle.
• The corpus luteum takes over during the last half of
the cycle to prepare the female reproductive tract for
pregnancy in case fertilization of the released egg
occurs.
 Effect of Gonadotropic hormones on the ovaries
• As in the male, gonadal function in the female is
directly controlled by the anterior gonadotropic
hormones (FSH & LH). These hormones in turn are
regulated by hypothalamic GnRH.
• In the absence of these hormones, the ovaries remain
inactive throughout the childhood. At the age of 9 to
12 years, the pituitary begins to secrete progressively
more FSH and LH, which leads to onset of normal
monthly sexual cycles beginning between the ages of
11 and 15 years.
• During each month of the female cycle, there is a
cyclical increase and decrease of both FSH and LH,
associated with several cyclical ovarian changes
along with uterine changes.
 Ovarian Follicular Growth - Follicular Phase
• When a female child is born, each ovum is surrounded by
a single layer of granulosa cells. The ovum with this
single layer of granulosa cell sheath is called a primordial
follicle.
• Throughout the childhood, the granulosa cells are
believed to secrete some maturation-inhibition-factors
that keep the ovum suspended in the primordial state in
the prophase stage of meiotic division.
• Then after puberty, FSH and LH from the anterior
pituitary begin to secrete in significant quantities. And
the ovaries together with some of the follicles within
them begin to grow.
• The first stage of follicular growth is moderate
enlargement of the ovum itself, which increases in
diameter twofold to threefold. Then follows growth of
additional layers of granulosa cells in some of the
follicles; these follicles are known as primary follicles.
 Development of Antrum
• Increased concentration of FSH (slightly greater) and LH cause
accelerated growth of 6 to 12 primary follicles each month. The
initial effect is proliferation of granulosa cells, giving rise to
many more layers of these cells.
• At this time, a second layer of cell mass is formed surrounding
the granulosa cells is called the theca. The layer of thecal cells
having the similar epithelioid characteristics of granulosa cells
are called theca interna and is also surrounded by another layer
of thecal cells is called theca externa.
• After the early proliferative phase of growth, the surrounding
mass of granulosa cells secrete a follicular fluid very rich in
estrogen and start to accumulate in a fluid filled cavity called the
antrum.
• Early growth of the follicle upto the antral stage is mainly
stimulated by the FSH alone but the latter stage of development
upto the mature follicle is depended on (i) high estrogen
production from the granulosa cells, (ii) increased production of
FSH and LH receptors.
 Development of Graafian follicle
• After a week or more of the growth but before ovulation occurs,
only one of the follicles begin to outgrow further and become the
ultimate mature Graafian follicle and the other remaining
follicles which has grown little bit but not final mature become
degenerated through a process called follicular atresia and these
follicles which undergone the process of atresia are called the
atretic follicles.
• The actual reason for the atresia is yet unknown but probable
reasons are the following: (i) the larger amounts of estrogen
from the rapidly growing follicle giving a negative signal to the
hypothalamus to depress FSH and LH to inhibit further growth
of the remaining follicles, (ii) rapidly growing follicle express
more numbers of FSH and LH receptors.
• This is the reason why only one ovum is destined to ovulate each
month of the cycle; this usually prevents more than one child
from developing with each pregnancy.
• The single follicle reaches a diameter of 1 to 1.5 centimeters at
the time of ovulation and is called the mature Graafian follicle.
 Ovulation – Release of mature ovum
• Ovulation in a woman who has a normal 28 day female sexual
cycle occurs 14 days after the onset of menstruation.
• LH is necessary for final follicular growth and ovulation. Without
this hormone, even when large quantities of FSH are available,
the follicle will not progress to the stage of ovulation.
• After 2 days before ovulation, the rate of secretion of LH by the
anterior pituitary gland increases markedly, rising to 6 to 10 fold
and peaking about 16 hours before ovulation. This high peak of
LH just before ovulation is called the LH surge.
• FSH also increases 2-3 fold at this time and both the FSH and LH
act synergistically to cause rapid swelling of the follicle during
the last few days before ovulation.
• At this time, LH also converts the follicular cells into
progesterone secreting cells and they begin to secrete
progesterone. Therefore, the rate of secretion of estrogen begins
to fall about 1 day before ovulation, while increasing amounts of
progesterone begin to be secreted.
• Ovulation will not take place in absence of pre-ovulatory surge.
• In response to LH surge, some changes take place:
• (i) The theca externa (the capsule of the follicle)
begins to release proteolytic enzymes from lysosomes
and these cause dissolution of the follicular capsular
wall and consequent weakening of the wall, resulting
in further swelling of the entire follicle and
degeneration of the stigma.
• (ii) Simultaneously, there is rapid growth of new blood
vessels into the follicle wall and also some amounts of
prostaglandins are secreted into the follicular tissues.
These two factors cause further swelling of the
follicle.
• Finally, the combination of follicle swelling and
simultaneous degeneration of the stigma causes the
rupture of the follicle with discharge of the ovum.
 Corpus Luteum - Luteal Phase
• During the first few hours after expulsion of the ovum from the
follicle, the remaining granulosa and theca internal cells rapidly
change into lutein cells
• They enlarge in diameter two or more times and become filled
with lipid inclusions that give them a yellowish appearance. This
process is called Luteinization and the total mass is called Corpus
Luteum. A well developed vascular supply also grows into the
corpus luteum.
• The granulosa cells in the corpus luteum become the major
source of progesterone and estrogen. The thecal cells primarily
form androgens and they are converted into female sex hormones
by the granulosa cells.
• Normally, corpus luteum grows to about 1.5 centimeters in
diameter reaching the stage of development 7 to 8 days after
ovulation and remain active about 12 days after ovulation. If
pregnancy does not take place, the corpus luteum begin to
degenerate and become whitish in color called the Corpus
Albicans. This is then replaced by connective tissue and over
month is absorbed.
Involution of Corpus Luteum and Onset of the next Ovarian Cycle
• Estrogen and progesterone both are secreted by the corpus
luteum have strong negative feedback effects on the anterior
pituitary to maintain very low level of FSH and LH.
• In addition, the lutein cells secrete small amounts of inhibin
hormone inhibits further FSH secretion. This low levels of
FSH and LH finally causes the corpus luteum to degenerate
completely in a process called involution of the corps
luteum.
• Final involution occurs at the end of exactly 12 days of
corpus luteum life, which is around 26th day of the normal
female sexual cycle, 2 days before menstruation begins.
• At this time, the sudden cessation of secretion of estrogen,
inhibin and progesterone from the corpus luteum removes
the feedback inhibition from the anterior pituitary, allowing
it to begin secreting FSH and LH again.
• This initiation of FSH and LH again from the anterior
pituitary now begins the next new round of ovarian cycle.
 Uterine Cycle
• The menstrual cycle of the human female is approximately 28 days long
and is numbered from the first day of the menses.
• Menstruation is the process in which the lining of the uterus is shed off
once during each cycle, a process that usually takes 3-5 days.
• Under the influence of increasing titer of estrogen, the endometrium of
the uterus increases in thickness reaching the width of 3 to 5 mm just
prior to ovulation. Stromal connective tissue cells proliferate and
extracellular collagen deposits are increased.
• In response to luteal phase progesterone level, uterine glands increase in
complexity from simple tubular elements to thick, coiled structures with
glandular lumen with secretory material.
• Spiral arteries within the endometrium become thickened and engorged
with blood.
• If implantation does not happen, lymphocytes begin to invade the
endometrium and by day 14, sloughing of the endometrium occurs due to
loss of ovarian steroid hormone support.
• In the absence of a hormonal support, the spiral arteries become
constricted and the blood lost from these arteries along with stromal
debris composes the bulk of menstrual flow.
 Vaginal Cycle
• In pre-pubertal and post-pubertal females, the vaginal
epithelium is thin, being composed of a few layers of
epithelial cells. In response to estrogens, this epithelium
proliferates and subsequently consists of many more layers
of epithelial cells.
• The histological features of vaginal epithelium change in a
characteristic manner during the menstrual cycle.
• Early in the cycle, the epithelium consists of rounded basal
cells. Maximum growth of the epithelium occurs during the
pre-ovulatory period.
• At this time, the basal cells are overlain with layers of more
flattened cells; the outermost cells are very flat and
keratinized and they fail to stain, thus indicating that they
are dead.
• Toward the end of luteal phase, the vaginal epithelium
becomes invaded with leukocytes and by the initiation of the
next cycle, cells of the outer layers of the epithelium are lost.
Discussion Session
Thank U