HPO axis and normal menstrual cycle Flashcards
Define Hypothalamic-Pituitary-Gonadal (HPG) axis?
Major signalling pathway of hypothalamus, pituitary gland and gonads (ovaries/testis) that regulates gender development in embryogenesis, sexual maturation, endocrine and exocrine function of mature gonads
What is the role of the HPG axis in embryogenesis?
Regulates gender development
What is the role of the HPG axis in adolescence?
Regulates sexual maturation
What is the role of the HPG axis in mature gonads?
Regulates exocrine and endocrine function
What term is used to refer to the HPG axis in females?
Hypothalamic-Pituitary-Ovarian (HPO) axis
What term is used to refer to the HPG axis in males?
Hypothalamic-Pituitary-Testicular (HPT)
Which 2 cycles are controlled by the HPO axis, to regulate female reproduction and menstruation?
Ovarian cycle
Uterine cycle
What are the 2 phases of the ovarian cycle, and what process occurs between these phases?
Follicular phase (day 1-14)
Ovulation
Luteal phase (day 15-28)
In the HPO axis, what hormone is produced in the hypothalamus, and what specific hypothalamic region is this produced in?
Gonadotropin-releasing hormone (GnRH)/lutenising-releasing hormone (LRH)
Produced by arcuate nucleus of hypothalamus
In the HPO axis, is all of the GnRH released at once from the arcuate nucleus of the hypothalamus?
No, GnRH is secreted by small body neurons in a pulsatile way (frequency of ~1 pulse hourly)
What brain structure is GnRH secreted into from the arcuate nucleus in the HPO axis, and why?
Median eminence: Structure at base of inferior hypothalamic surface that has no blood-brain barrier
No blood-brain barrier allows this to be interface between neural and peripheral endocrine systems
In the HPO axis, which brain structure is GnRH transported to from the median eminence?
Anterior pituitary gland
In the HPO axis, which transportation system is used to transport GnRH from median eminence to anterior pituitary gland, and explain this process?
Hypophyseal portal system: Vascular capillary system that connects hypothalamus and anterior pituitary gland
GnRH secreted into median eminence which are released into primary plexus of hypophyseal capillary bed, then are transported across hypophyseal portal system to secondary plexus to be released into anterior pituitary gland
In the HPO axis, what receptors do GnRH molecules bind to in the anterior pituitary gland, and what does this stimulate?
GnRH binds to receptors of gonadotropic cells to stimulate secretion of gonadotropins
Define gonadotropin, and give 2 examples?
Glycoprotein hormones secreted by anterior pituitary gonadotropic cells of vertebrates
Eg. Follicle-stimulating Hormone (FSH), Luteinising Hormone (LH)
In the HPO axis, which 2 gonadotropins are produced in the anterior pituitary gland in response to GnRH?
Follicle-stimulating Hormone (FSH)
Luteinising Hormone (LH)
In the follicular phase, what is the first structure of folliculogenesis, and define this structure?
Primordial follicle
Immature oocytes surrounded by layer of flattened squamous granulosa cells, formed from primordial germ cells
Define zona pellucida?
Thick extracellular matrix membrane surrounding oocyte
In the follicular phase, what 3 changes occur so that the primordial follicle becomes a primary follicle, and define primary follicle?
Primary follicle: Oocyte surrounded by cuboidal granulosa cells that are arranged in a single layer
Oocyte increases in size
Zona pellucida forms
Granulosa cells proliferate, change from squamous to cuboidal
Define secondary follicle, and what 2 changes occur in a primary follicle to become the secondary follicle, during the follicular phase?
Secondary follicle: primary oocyte surrounded by multiple layers of cuboidal granulosa cells
Cuboidal granulosa cells proliferate to change from single to multiple layers
Surrounding ovary stromal cells differentiate into theca cells
Which 2 receptors are expressed by granulosa cells when secondary follicles develop, and what 2 hormones are produced by them?
LH and FSH receptors which stimulates production of oestrogen and little progesterone by secondary follicles
What 3 hormones are synthesised by granulosa cells of secondary follicles, in follicular phase?
Oestrogen
Progesterone
Inhibins
In the follicular phase, what 2 changes occur to the secondary follicle to become a tertiary/antral follicle?
Granulosa cells produce antrum (fluid-filled space in follicle centre due to fluid secretion from granulosa cells)
Some granulosa cells become corona radiata/cumulus cells (granulosa cells immediately surrounding zona pellucida)
Why are primordial, primary and secondary follicles described as preantral?
They don’t have an antrum
In the follicular phase, what causes FSH and LH production in the anterior pituitary gland to be inhibited?
Oestrogen and inhibins have negative feedback effect on hypothalamus and anterior pituitary gland, so as levels increase the release of LH and FSH is inhibited.
In the follicular phase, how is it determined which tertiary follicle will mature and become the graafian follicle?
Tertiary follicles with fewest FSH receptors regress and degenerate (follicular atresia) until one dominant follicle is left to mature, this becomes the graafian follicle
When in the follicular phase is there a negative feedback effect on the hypothalamus and anterior pituitary gland, leading to decreased FSH and LH levels?
Since they became secondary follicles, they have been producing oestrogen and inhibins which inhibit production of FSH and LH due to negative feedback effect of rising oestrogen level.
In the follicular phase, how does the antrum change so that the tertiary follicle becomes the graafian/preovulatory follicle?
Antrum enlarges and fully surrounds oocyte except from area of granulosa cells that attach oocyte to follicle
In the follicular phase, what process occurs after the graafian follicle has formed?
Ovulation
Define ovulation?
Process of releasing secondary oocyte from graafian follicle in alternating ovaries (typically one oocyte released per cycle)
What gonadotropin has very high levels which causes ovulation, and how is this high level produced?
LH surge (very high level) causes ovulation
Oestrogen level is high enough to cause shift from negative feedback to positive feedback effect on hypothalamus and anterior pituitary, so LH surge occurs (very high level mid-cycle)
During ovulation, how does the LH surge cause the secondary oocyte to be released from the graafian follicle?
LH surge activates inflammatory prostaglandin release which causes graafian follicle to rupture and oocyte is released into abdominal cavity
Define mittelschmerz?
Lower abdominal pain during ovulation
Which 2 hormones is the luteal phase mostly regulated by?
Progesterone
LH
Immediately after ovulation, what structure forms and explain how the graafian follicle develops into this, in the luteal phase?
Corpus haemorrhagicum:
Ruptured graafian follicle fills with blood clot
Define corpus luteum?
Temporary endocrine gland resulting from remaining granulosa and theca cells in ruptured graafian follicle after ovulation
In the luteal phase, explain how the corpus haemorrhagicum becomes the corpus luteum?
Still has blood clot centre, but surrounding granulosa and theca lutein cells increase to change corpus haemorrhagicum into corpus luteum
In the luteal phase, what stimulates formation of the corpus structures, and what maintains them?
Stimulated by LH surge, then are maintained by LH level
What are the 2 ways in which corpus luteum prepares the endometrium for implantation, in the luteal phase?
Secretes high level of progesterone
Secretes low level of oestrogen
In the luteal phase, what is the effect of the secretion of oestrogen and progestorone by corpus luteum on the HPO axis, in the luteal phase?
Progesterone and oestrogen secreted have negative feedback effect on hypothalamus and anterior pituitary gland so inhibits FSH and LH release
In the luteal phase, if fertilisation occurs what structure does the corpus luteum change into and why?
corpus luteum graviditatis
to maintain pregnancy until placenta fully takes over
In the luteal phase, if fertilisation doesn’t occur what happens to the corpus luteum and what resulting structure is formed?
Corpus luteum degenerates for 12-14 days due to decreased LH levels
Causes formation of corpus albicans (scar tissue that is the regressed form of corpus luteum)
In the luteal phase, how does formation of the corpus albicans stimulate the menstrual cycle to restart?
Decreasing progesterone and oestrogen levels (due to lack of corpus luteum) end negative feedback effect on hypothalamus and anterior pituitary gland, so that FSH and LH can be released and menstrual cycle restarts
Why does the uterine cycle need to regulate endometrial changes?
To prepare for embryo implantation
During the follicular phase of the ovarian cycle, which 2 phases of the uterine cycle occur at the same time?
Menstrual phase (days 1-5) and proliferative phase (days 5-14)
During the luteal phase of the ovarian cycle, which phase of the uterine cycle occurs at the same time?
Secretory phase (days 15-28)
When does menses occur within the uterine cycle?
Menses happens at end of uterine cycle (during menstrual phase) but the first day of bleeding is still defined as day 1 of uterine cycle
What event defines the day 1 of the uterine cycle?
First day of bleeding on period
In the proliferative phase, how does the corresponding follicular phase of the ovarian cycle stimulate proliferation?
Oestrogen produced by ovarian follicular phase stimulates proliferation
In the proliferative phase, which endometrial layer is stimulated to thicken by oestrogen, and how thick does the layer become?
Stimulates proliferation of all cell types in endometrial basal layer (stratum basalis) until it becomes ~2mm thick
What are the 2 effects of oestrogen on cervical mucus, and what is the overall change that this causes, in the proliferative phase?
Decreases cervical mucus viscosity
Increases cervical mucus volume
Cervical mucus changes from thick plug (blocks the cervix) to thin, slippery mucus that can be penetrated by spermatozoa
In the secretory phase, what 2 changes does progesterone stimulate the uterine glands to undergo and why?
Uterine glands enlarge
Uterine glands secrete glycogen
These changes support implantation and increase embryo viability
In the secretory phase, what is the effect of progesterone on endometrial changes?
Progesterone inhibits endometrial layer growth
In the secretory phase, how does the corresponding luteal phase of the ovarian cycle stimulate uterine glands?
Uterine glands stimulated by progesterone produced in luteal phase
In the secretory phase, how does oestrogen stimulate the growth of new arteries?
Oestrogen stimulates endometrial spiral arteries to develop from straight basal arteries (originating in myometrium under basal endometrium) by increasing size and coil, and supply middle and superficial (functional) endometrial layers
In the secretory phase, which endometrial layers are supplied by the spiral arteries, and how thick is the endometrium now?
Supply functional layers: middle and superficial
Endometrium now ~5mm thick
What are the 2 effects of progesterone on cervical mucus, and what is the overall change that this causes, in the proliferative phase?
Increases cervical mucus viscosity
Decreases cervical mucus volume
Cervical mucus changes from thin, slippery mucus to thick plug that blocks cervix and protects embryo
Define endometrial hyperplasia, and how does oestrogen cause this?
Endometrial hyperplasia: condition where there is irregular thickening of endometrium
Oestrogen stimulates epithelial hyperplasia and hypertrophy
In the secretory phase, if no fertilisation occurs, how does changes in the corpus luteum stimulate endometrial spiral arteries and stratum functionalis?
Corpus luteum regresses so less progesterone and oestrogen is produced
Causes spinal arteries to constrict/spasm
Causes endometrial functional layers becomes hypoxic (ischaemic necrosis)
In the menstrual phase, what happens to the spiral arteries?
Spiral arteries dilate and bleed into necrotic stratum functionalis of endometrium
In the menstrual phase, which 3 substances initially form a clot in the uterine cavity?
Necrotic stratum functionalis
Tissue fluid
Blood
In the menstrual phase, what molecules prevent further clotting in the uterine cavity, so that it can all be expelled in menses?
Fibrinolysins liquefy the forming clot
In the menstrual phase, which 2 substances have their receptors upregulated by oestrogen, and how does this stimulate smooth muscle?
Oestrogen upregulates receptors for oxytocin and prostaglandin
which stimulate uterine (smooth muscle) contractions
This expels blood which can cause dysmenorrhoea (pain)
How does progesterone stimulate smooth muscle in the uterus
Progesterone downregulates receptors so causes uterine relaxation
