Physiology II: L47, Menstrual Cycle
what causes increased inhibin secretion?
As follicles develop and the number of their granulosa cells increases, also the output of inhibin increases. Therefore, during the follicular phase, accumulation of inhibin will induce a decline in the release of FSH. In essence, inhibin communicates to the pituitary how advanced the development of the follicles is. This effect is very important for the selection of the dominant antral follicle.
when does the menstrual cycle begin?
By convention, the menstrual cycle begins with the first day of menstrual bleeding (menstruation).
stages of the follicular phase of the menstrual cycle
Day 1-4/5: Pre-antral follicles mature into antral follicles Day 4/5-7: A decline in the pituitary release of FSH induces death of all but one of the antral follicles of the cohort; the healthiest and more capable of producing estrogen survives (dominant antral follicle) Day 7-14: The dominant antral follicle develops further and drastically increases its production of estrogen, so plasma estrogen levels rise
luteal phase of the menstrual cycle
Day 16-25: the Graafian follicle is modified into granulosa and theca cells of the corpus luteum by the still elevated LH Day 25-28: If fertilization has not occurred, the corpus luteum undergoes luteolysis (apoptosis), and its production of hormones ceases. This concludes one menstrual cycle and allows for another one to begin. On the other hand, if fertilization has occurred, the corpus luteum survives and pregnancy can progress.
timeline of the menstrual cycle
Day 1: bleeding starts Day 1-7: preantral follicles converted into antral follicles by FSH + estrogen Day 7: selection of dominant follicle Day 7-14: dominant antral follicle develops + secretes estrogen Day 15: ovulation, LH surge Day 16-25: Graafian follicle becomes corpus luteum, secretes progesterone and estrogen Day 25: degeneration of the corpus luteum Day 25-28: progesterone and estrogen decrease, sloughing
follicular phase of the menstrual cycle
During the first two weeks of the menstrual cycle, a cohort of pre-antral follicles starts developing under the influence of pituitary hormones (esp FSH). Follicles produce hormones. In this first half of the menstrual cycle, estrogen is particularly important, because it supports the development of follicles and also induces changes in the reproductive tract. For this reason, it is said that the follicular phase is estrogen dominated.
what induces kisspeptin release?
Estrogen (working in positive feedback mode) can stimulate the release of Kiss-1 and GnRH (also reduces kisspeptin release when it is in its negative feedback loop)
FSH and LH
FSH and LH belong to the same glycoprotein family; have similar structures; both activate a G-protein/c-AMP system in their target cells; FSH and LH work on different parts of the follicle but are both required in the synthesis of estrogens; participate in the development and activity of follicles and corpus luteum
function of inhibin
controls the release of FSH via negative feedback; communicates to the pituitary how advanced the development of the follicles is
when does the LH surge occur?
day 15, during the ovulatory phase of the menstrual cycle
menstrual phase of the menstrual cycle (uterine viewpoint)
days 1-5; When the hormonal support provided by the corpus luteum is withdrawn, the endometrium becomes necrotic and is expelled from the uterus. This by convention coincides with the beginning of a new cycle.
secretory phase of the menstrual cycle (uterine viewpoint)
days 16-28; Under the effect of progesterone, proliferation stops, and the glands that are embedded in the endometrium start releasing nutrients, growth factors, and cytokines that favor implantation and the establishment of pregnancy. Progesterone also favors relaxation of the smooth muscles of the uterus and fallopian tubes (helps the descent of the blastocyst in the uterus and creates a stable surface for docking onto the endometrium).
proliferative phase of the menstrual cycle (uterine viewpoint)
days 5-15; Under the stimulation of increasing levels of estrogen, the endometrium grows back. Estrogen also favors the contractility of the smooth muscle cells of the uterus and fallopian tubes (helps progression of sperm toward the site of fertilization).
endometrium
epithelial lining of hte uterus
what are the uterus and fallopian tubes sensitive to?
epithelium and smooth muscle cells of the uterus and fallopian tubes are sensitive to estrogen and progesterone; the behavior of these tissues will vary during the menstrual cycle
which hormone dominates the different stages of the menstrual cycle?
follicular phase dominated by estrogen; luteal phase dominated by progesterone
what does GnRH control?
the changing pulse frequency of GnRH secretion determines whether FSH or LH is released more abundantly from the gonadotrophs; low frequency of GnRH pulses = FSH favored; high frequency of GnRH pulses = LH favored
conceptus
the zygote that has evolved into a blastocyst
kisspeptin and GnRH
varying amounts of kiss-1 released from the pulse generating system of the hypothalamus affect the release of GnRH from the neurosecretory cells of the hypothalamus and ultimately control the activity of the reproductive system; you need kisspeptin to release GnRH
three phases of the menstrual cycle + how long each phase is
1.) Follicular: ~3-14 days long (average) 2.) Ovulatory: ~1 day long 3.) Luteal: 13-14 days long
what does the menstrual cycle ultimately lead to?
1.) Maturation of the Graafian follicle 2.) Ovulation 3.) Alterations of the female reproductive system that favor fertilization and implantation of the conceptus
ovulatory phase of the menstrual cycle
Lasts just one day (Day 15) Luteinizing Hormone (LH) surge: extremely high levels of estrogen induce massive release of LH from the pituitary Development of the Graafian follicle and completion of first meiotic division: direct consequences of the LH surge Ovulation: The Graafian follicle bursts and releases the oocyte
non-pulsatile GnRH administration
Continuous administration of non-pulsatile GnRH decreases FSH and LH secretion. As soon as the treatment is suspended and GnRH resumes its pulsatile release, FSH and LH return to normal levels.
what concludes the menstrual cycle?
If fertilization has not occurred, the corpus luteum undergoes luteolysis (apoptosis), and its production of hormones ceases. This concludes one menstrual cycle and allows for another one to begin.
how does kisspeptin regulate GnRH?
Kiss-1 regulates the amplitude and frequency of the pulsatile release of GnRH
Kisspeptin
Kiss-1; a peptide hormone made by the pulse generator system in the hypothalamus; regulates the amplitude and frequency of the pulsatile release of GnRH
when does hormone output from the corpus luteum peak?
The hormonal output of the corpus luteum peaks at around day 21 of the menstrual cycle.
what starts off the menstrual cycle?
The menstrual cycle is set in motion by the hormones of the hypothalamus-pituitary axis
how long is the menstrual cycle?
The menstrual cycle lasts in average 28 days (with individual variations).
purpose of the corpus luteum
The purpose of the corpus luteum is to produce large amounts of hormones (estrogen and progesterone). Makes more progesterone which is the most important for implantation and maintenance of pregnancy.
where are LH and FSH made?
gonadotroph cells of anterior pituitary
GnRH
gonadotropin releasing hormone; a trophic peptide hormone released by neurons in the hypothalamus; travels in the portal vessels that connect the hypothalamus to the anterior pituitary; induces the release of gonadotropins (FSH and LH).
what inhibits kisspeptin release?
high stress, hypothyroidism, progesterone, estrogen (working in negative feedback mode), and insufficient caloric intake are strong inhibitors of the release of Kiss-1 (and consequently of GnRH)
what makes GnRH?
hypothalamus
pulse generator system
in the hypothalamus; two nuclei that make kisspeptin; processes information concerning the health and nutritional status of the body; its neurons express receptors for hormones like cortisol (stress), thyroid hormones and insulin (metabolic status of the body), estrogen and progesterone (ovarian activity), and many others; responds to these inputs by releasing varying amounts of kiss-1
LH receptors
initially located only on theca cells, but later in the menstrual cycle appear also on granulosa cells
where is kisspeptin made?
produced in two regulatory nuclei (groups of neurons) in the hypothalamus which are known as the pulse generator system
FSH receptors
located exclusively on granulosa cells
which GnRH pulse speed favors what?
low frequency of GnRH pulses = FSH favored high frequency of GnRH pulses = LH favored
how does constant GnRH administration work?
lowers of LH and FSH; non-pulsatile administration of GnRH decreases the number of GnRH receptors on the gonadotroph cells (cells that produce gonadotropins: LH, FSH) of the anterior pituitary which becomes less sensitive to GnRH (down regulation)
three uterine stages of the menstrual cycle and when they are
menstrual phase (day 1-5) proliferative phase (day 5-15) secretory phase (day 16-28)
inhibin
peptide hormone; secreted by granulosa cells of follicles and corpus luteum; inhibin release is stimulated by FSH; inhibin in turn controls the release of FSH via negative feedback
GnRH secretion
pulsatile; amplitude and frequency of the GnRH release pulses are crucial for appropriate release of pituitary hormones during the menstrual cycle; amplitude and frequency of GnRH release are controlled by kisspeptin
seven hormones that control of the menstrual cycle
released by the hypothalamus or pituitary (brain): kisspeptin (Kiss-1) gonadotropin releasing hormone (GnRH) follicle stimulating hormone (FSH) luteinizing hormone (LH) released by the follicles/corpus luteum (ovaries): Inhibin Estrogen Progesterone
what is continuous GnRH administration used to treat?
some forms of precocious puberty (because lowers both LH and FSH), fibroids, and endometriosis; causes suppression of the hypothalamus-pituitary-gonadal axis (and, ultimately, reduction in the release of estrogen) which is beneficial in these conditions
FSH function
stimulates granulosa cells to make inhibin during the entire menstrual cycle; required in the synthesis of estrogens; participates in the development and activity of follicles and corpus luteum
LH function
stimulates granulosa cells to produce progesterone during the luteal phase; required in the synthesis of estrogens; participates in the development and activity of follicles and corpus luteum
