PHY3181 Lecture Notes - Lecture 1: Oogenesis, Gonadotropin, Mitosis
30 Jun 2018
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Lecture 6: female reproductive endocrinology
Note that the ovarian cycle and the menstrual
cycle are happening at the same time – the
menstrual cycle is occurring in the
endometrium.
The HPG axis
• Hypothalamus GnRH synthesis
• Median eminence GnRH storage/
release
• Portal blood vessels GnRH transport
• Anterior pituitary GnRH action
• LH and FSH released into bloodstream
Ovarian cycle
The recruitement of primordial follicles to
become primary follicles is a spontaneous
event (LH and FSH are not required for the
initial recruitment of primordial follicles).
FSH is involved in follicular recruitment
(primary to secondary). The mature follicle
must have LH receptors (there is an LH pulse
that induces ovulation).
The ruptured follicle will undergo luteinisation
corpus luteum. The CL is the primary site of
progesterone production. Progesterone levels
are very high in the luteal phase of the cycle.
This is because at the same time progesterone
is needed to mature the endometrium should
there be an implantation.
Menstrual (uterine) cycle
Follicular phase of the ovarian cycle: lots of
estrogen
Luteal phase of the ovarian cycle: lots of
progesterone. Progesterone is the key
hormone that maintains preganncy. Note that
estrogen is also produced by the corpus
luteum.
While the ovarian cycle is dirven by hormones
released by the anterior pituitary, the uterine
cycle is driven by steroid hormones rleased by
the ovary. Cyclic changes of the endometrium
in response to hormone. Endometrial changes
are coordinated with the ovarian cycle.
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The uterus
Th uterine wall is composed of three layers:
• Perimetrium: outermost layer
• Myometrium: bulky, muscular middle
layer (contracts to expel the baby)
• Endometrium: mucosal inner layer
o Allows for implantation of the
fertilised egg
o Functional layer: undergoes
cyclic changes due to ovarian
hormones and is shed during
menstruation
o Basal layer: unresponsive to
ovarian hormones
The menstrual uterine cycle
Note that the length of individual cycles is very
variable. What is fixed: 14 days of the luteal
phase (this is the most fixed time)
Day 1 - 5: menstrual phase (menses) is the
shedding of the functional layer of the
endometrium. Estrogen and progesterone
levels are low (at this time the follicle is not
mature yet). The amount of days in the
menstrual phase is variable.
Day 6 - 14: pre-ovulatory/ proliferative phase
is the rebuilding of the functional layer of the
endometrium. Proliferation of glandular
epithelial cells, stroma and blood vessels is
occurring. Cervical mucous becomes less
viscous and sticky – allows entry of sperm. The
proliferative phase is stimulated and sustained
by ovarian estrogens (oestrogen levels are
increasing). Ovulation occurs at the end of this
phase.
Day 15 – 28: secretory (post-ovulatory phase)
begins immediately after ovulation.
Endometrium prepares for implantation
(glands enlarge, arteries elongate and nutrition
glycogen is secreted). The secretory phase
requires progesterone and estrogens from the
corpus luteum. If fertilisation does not occur,
the CL degenerates low progesterone leads
to spasm of the arteries and low oxygen levels
– blood enters the fragmented capillaries and
menses begins again.
Note that if there is a pregnancy the embryo
itself makes HGC tells the ovary to keep
making progesterone from the CL.
Note that over the cycle the GnRH pulse
frequency will change to change the amounts
of hormones to enable ovulation to occur
Biosynthesis of steroid hormones
The ovary will turn cholesterol into
pregnenolone progesterone.
Progesterone or other pathways will then
make testosterone. The testosterone can then
be converted to estrogen. (the ovary will make
testosterone before it will make estrogen)
Where is oestradiol synthesised?
In the granulosa cells via the theca cells. We
have to make testosterone before we can
make estrogen. estrogen production is a two
step process occurring in two cells.
1. LH acts on the thecal cells – respond to
LH and make testosterone
2. The testosterone is secreted from the
thecal cell across the basal lamina into
the granulosa cell
a. Aromatase converts
testosterone to estrogen
Note the steroid production is all happening
within the follicle.
Where is progesterone synthesised?
By the corpus luteum.
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Steroid hormones control GnRH signalling
• Estrogen induces negative feedback
most of the cycle
• Estrogen switches to positive feedback
prior to ovulation (days 12-14)
• Causes surge of LH and ovulation
• Progesterone not involved in positive
feedback, but it must be low to allow
positive feedback of estrogen to act on
GnRH
Inhibin A and Inhibin B – ovarian protein
hormones
• Produced by the granulosa cells of the
ovary
• They are peptide hormones
(glycoproteins)
• The alpha subunit is in both
• They have different beta subunits
• Both have different biological actions
• Inhibin levels change across the
menstrual cycle
• Inhibin A is elevated in the luteal phase
of the menstrual cycle
• Inhibin B is maximal in mid follicular
phase of the menstrual cycle
Inhibin acts to inhibin FSH-beta. Inhibin B is
more effective at inhibiting FSH.
• There is an inverse relationship
between inhibin B and FSH
• FSH stimulates follicles to develop in
luteal phase of preceding cycle
• The developing follicles produce
increasing levels of inhibin B during
follicular phase of cycle
• Inhibin B acts on the pituitary to inhibit
FSH
• As non-dominant follicles die by
atresia, inhibin B levels fall – remove
inhibition on FSH.
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Hormonal influences in females
Estrogens are similar to testosterone in males.
At puberty they:
• Promote oogenesis
• Increase growth of the vagina, uterus
and fallopian tubes
• Induce initial growth spurt but then
close the epiphyses of long bones
Document Summary
Note that the ovarian cycle and the menstrual cycle are happening at the same time the menstrual the endometrium. is occurring cycle in. The hpg axis: hypothalamus gnrh synthesis, median eminence gnrh storage/ release, portal blood vessels gnrh transport, anterior pituitary gnrh action. The recruitement of primordial follicles to become primary follicles is a spontaneous event (lh and fsh are not required for the initial recruitment of primordial follicles). is involved in follicular recruitment. The mature follicle must have lh receptors (there is an lh pulse that induces ovulation). The cl is the primary site of progesterone production. Progesterone levels are very high in the luteal phase of the cycle. This is because at the same time progesterone is needed to mature the endometrium should there be an implantation. Follicular phase of the ovarian cycle: lots of estrogen. Luteal phase of the ovarian cycle: lots of progesterone. Note that estrogen is also produced by the corpus luteum. is.
