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Reproductive system-4
Dr. Sai Sailesh Kumar G
Associate Professor
Department of Physiology
RDGMC
Regulation of ovarian cycle
 The ovary has two related endocrine units:
1. the estrogen secreting follicle during the first half of
the cycle and
2. the corpus luteum, which secretes both progesterone
and estrogen, during the last half of the cycle.
Regulation of ovarian cycle
 Unlike in the male, however, control of the female gonads is
complicated by the cyclic nature of ovarian function.
 For example, the effects of FSH and LH on the ovaries
depend on the stage of the ovarian cycle.
 Estrogen exerts negative-feedback effects during
part of the cycle and positive-feedback effects
during another part of the cycle, depending on the
concentration of estrogen.
Control of follicular function
 Step-1: The early stages of preantral follicular growth and
oocyte maturation precede the follicular phase and do not
require gonadotropic stimulation.
 Step-2: Hormonal support is required, however, for further
follicular development and antrum formation and for
estrogen secretion.
 Step-3: Estrogen
 Step-4: FSH
 Step-5: and LH are all needed.
Control of follicular function
 FSH induces antrum formation.
 Both FSH and estrogen stimulate proliferation of the
granulosa cells.
 Both LH and FSH are required for synthesis and secretion of
estrogen by the follicle.
 But these hormones act on different cells and at different
steps in the estrogen production pathway.
Control of follicular function
 Step-6: Because low basal levels of FSH are sufficient to
promote this final conversion to estrogen
 Step-7: The rate of estrogen secretion by the follicle
primarily depends on the circulating level of LH, which
continues to rise during the follicular phase
 Furthermore, as the follicle continues to grow, more
estrogen is produced simply because more estrogen
producing follicular cells are present.
Control of follicular function
 Step-8: Part of the estrogen produced by the growing follicle
is secreted into the blood and is responsible for the steadily
increasing plasma estrogen levels during the follicular
phase
 The remainder of the estrogen remains within the follicle,
contributing to the antral fluid and stimulating further
granulosa cell proliferation.
Control of follicular function
 The secreted estrogen
 Acts on the sex-specific tissues such as the uterus
 inhibits the hypothalamus and anterior pituitary in typical
negative-feedback fashion.
 Estrogen selectively inhibits FSH secretion by the gonadotropes.
 Another contributing factor to the fall in FSH during the follicular
phase is secretion of inhibin by the follicular cells.
 Inhibin preferentially inhibits FSH secretion by acting at the
anterior pituitary.
Control of follicular function
 The decline in FSH secretion brings about atresia of all but
the single dominant, most mature of the developing follicles.
 Follicle which has higher sensitivity (more receptors) will
only survive.
 When estrogen offers negative feedback why LH secretion
is not inhibited??
Control of follicular function
 Estrogen alone cannot completely suppress LH secretion
 To completely inhibit tonic LH secretion, both estrogen and
progesterone are required.
 Because progesterone does not appear until the luteal
phase of the cycle, the basal level of circulating LH slowly
increases during the follicular phase.
Control of ovulation
 Step-9: Ovulation and subsequent luteinization of the ruptured follicle
are triggered by an abrupt, massive increase in LH secretion.
 This LH surge brings about four major changes in the follicle:
1. Step-10: It halts estrogen synthesis by the follicular cells.
2. It reinitiates meiosis in the mature follicle’s oocyte by blocking
release of oocyte maturation inhibitor produced by the granulosa
cells. This substance is responsible for arresting meiosis in the
primary oocytes once they are wrapped within granulosa cells in the
fetal ovary.
Control of ovulation
3. Step-11: It triggers production of local prostaglandins, which
induce ovulation by promoting vascular changes that cause
rapid follicular swelling while inducing enzymatic digestion of
the follicular wall. Together, these actions lead to rupture of the
weakened wall that covers the bulging follicle.
Control of ovulation
4. Step-12: It causes differentiation of follicular cells into luteal
cells. Because the LH surge triggers both ovulation and
luteinization, formation of the corpus luteum automatically
follows ovulation.
4. Step-13: Thus, the midcycle burst in LH secretion is a
dramatic point in the cycle; it terminates the follicular phase
and initiates the luteal phase.
Who triggers LH surge??
 Estrogen
 The LH surge is triggered by a positive-feedback effect.
 moderate level of estrogen early in the follicular phase inhibits LH
secretion
 the high level of estrogen that occurs during peak estrogen
secretion late in the follicular phase stimulates LH secretion and
initiates the LH surge
 The LH surge lasts for about a day at midcycle, just before
ovulation.
Luteal phase
 Step-14: LH levels are suppressed
 Step-15: By increase in the release of progesterone from
corpus leuteum under the influence of LH
 Estrogen and progesterone both suppress LH secretion by
inhibiting the ARC nucleus kiss1 neurons
Control of corpus luteum
 Step-15: Under the influence of LH, the CL secretes both
progesterone
 Step-16: and estrogen
 The plasma progesterone level increases for the first time during
the luteal phase.
 No progesterone is secreted during the follicular phase (except for
a small amount a few hours before ovulation).
 Therefore, the follicular phase is dominated by estrogen and the
luteal phase by progesterone.
Estrogen levels
 Step-10: A transitory drop in the level of circulating estrogen
occurs at midcycle.
 The estrogen-secreting follicle meets its demise at
ovulation.
 The estrogen level climbs again during the luteal phase
because of the CL’s activity, although it does not reach the
same peak as during the follicular phase.
 What happen if it reach peak?
Luteal phase
 LH surge
 Moderate levels of estrogen – negative feedback
 High levels of estrogen – positive feedback and LH surge
 Step-17: Progesterone, which dominates the luteal phase,
powerfully inhibits LH secretion as well as FSH secretion by
acting at both the hypothalamic ARC nucleus and the anterior
pituitary.
 Furthermore, the luteal cells secrete inhibin, which selectively
inhibits FSH secretion.
Luteal phase
 Why it is important to inhibit FSH and LH in luteal phase???
Luteal phase
 If not inhibited there may be maturation and ovulation of
another follicle in luteal phase.
Luteal phase
 Step-18: The corpus luteum functions for an average of 2
weeks and then degenerates if fertilization does not occur.
 The mechanisms that govern degeneration of the CL are not
fully understood.
 May be due to fall in LH
 Demise of the CL terminates the luteal phase and sets the
stage for a new follicular phase.
Luteal phase
 As the CL degenerates, plasma progesterone (step 19) and
estrogen (step 20) levels fall rapidly because these
hormones are no longer being produced.
 Withdrawal of the inhibitory effects of these hormones on
the hypothalamus allows FSH (step 21) and tonic LH (step
22) secretion to modestly increase again.
 New follicular phase begins.
THANK YOU

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Reproductive system 4

  • 1. Reproductive system-4 Dr. Sai Sailesh Kumar G Associate Professor Department of Physiology RDGMC
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  • 5. Regulation of ovarian cycle  The ovary has two related endocrine units: 1. the estrogen secreting follicle during the first half of the cycle and 2. the corpus luteum, which secretes both progesterone and estrogen, during the last half of the cycle.
  • 6.
  • 7. Regulation of ovarian cycle  Unlike in the male, however, control of the female gonads is complicated by the cyclic nature of ovarian function.  For example, the effects of FSH and LH on the ovaries depend on the stage of the ovarian cycle.  Estrogen exerts negative-feedback effects during part of the cycle and positive-feedback effects during another part of the cycle, depending on the concentration of estrogen.
  • 8. Control of follicular function  Step-1: The early stages of preantral follicular growth and oocyte maturation precede the follicular phase and do not require gonadotropic stimulation.  Step-2: Hormonal support is required, however, for further follicular development and antrum formation and for estrogen secretion.  Step-3: Estrogen  Step-4: FSH  Step-5: and LH are all needed.
  • 9. Control of follicular function  FSH induces antrum formation.  Both FSH and estrogen stimulate proliferation of the granulosa cells.  Both LH and FSH are required for synthesis and secretion of estrogen by the follicle.  But these hormones act on different cells and at different steps in the estrogen production pathway.
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  • 12. Control of follicular function  Step-6: Because low basal levels of FSH are sufficient to promote this final conversion to estrogen  Step-7: The rate of estrogen secretion by the follicle primarily depends on the circulating level of LH, which continues to rise during the follicular phase  Furthermore, as the follicle continues to grow, more estrogen is produced simply because more estrogen producing follicular cells are present.
  • 13. Control of follicular function  Step-8: Part of the estrogen produced by the growing follicle is secreted into the blood and is responsible for the steadily increasing plasma estrogen levels during the follicular phase  The remainder of the estrogen remains within the follicle, contributing to the antral fluid and stimulating further granulosa cell proliferation.
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  • 15. Control of follicular function  The secreted estrogen  Acts on the sex-specific tissues such as the uterus  inhibits the hypothalamus and anterior pituitary in typical negative-feedback fashion.  Estrogen selectively inhibits FSH secretion by the gonadotropes.  Another contributing factor to the fall in FSH during the follicular phase is secretion of inhibin by the follicular cells.  Inhibin preferentially inhibits FSH secretion by acting at the anterior pituitary.
  • 16. Control of follicular function  The decline in FSH secretion brings about atresia of all but the single dominant, most mature of the developing follicles.  Follicle which has higher sensitivity (more receptors) will only survive.  When estrogen offers negative feedback why LH secretion is not inhibited??
  • 17. Control of follicular function  Estrogen alone cannot completely suppress LH secretion  To completely inhibit tonic LH secretion, both estrogen and progesterone are required.  Because progesterone does not appear until the luteal phase of the cycle, the basal level of circulating LH slowly increases during the follicular phase.
  • 18. Control of ovulation  Step-9: Ovulation and subsequent luteinization of the ruptured follicle are triggered by an abrupt, massive increase in LH secretion.  This LH surge brings about four major changes in the follicle: 1. Step-10: It halts estrogen synthesis by the follicular cells. 2. It reinitiates meiosis in the mature follicle’s oocyte by blocking release of oocyte maturation inhibitor produced by the granulosa cells. This substance is responsible for arresting meiosis in the primary oocytes once they are wrapped within granulosa cells in the fetal ovary.
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  • 20. Control of ovulation 3. Step-11: It triggers production of local prostaglandins, which induce ovulation by promoting vascular changes that cause rapid follicular swelling while inducing enzymatic digestion of the follicular wall. Together, these actions lead to rupture of the weakened wall that covers the bulging follicle.
  • 21. Control of ovulation 4. Step-12: It causes differentiation of follicular cells into luteal cells. Because the LH surge triggers both ovulation and luteinization, formation of the corpus luteum automatically follows ovulation. 4. Step-13: Thus, the midcycle burst in LH secretion is a dramatic point in the cycle; it terminates the follicular phase and initiates the luteal phase.
  • 22. Who triggers LH surge??  Estrogen  The LH surge is triggered by a positive-feedback effect.  moderate level of estrogen early in the follicular phase inhibits LH secretion  the high level of estrogen that occurs during peak estrogen secretion late in the follicular phase stimulates LH secretion and initiates the LH surge  The LH surge lasts for about a day at midcycle, just before ovulation.
  • 23.
  • 24. Luteal phase  Step-14: LH levels are suppressed  Step-15: By increase in the release of progesterone from corpus leuteum under the influence of LH  Estrogen and progesterone both suppress LH secretion by inhibiting the ARC nucleus kiss1 neurons
  • 25.
  • 26. Control of corpus luteum  Step-15: Under the influence of LH, the CL secretes both progesterone  Step-16: and estrogen  The plasma progesterone level increases for the first time during the luteal phase.  No progesterone is secreted during the follicular phase (except for a small amount a few hours before ovulation).  Therefore, the follicular phase is dominated by estrogen and the luteal phase by progesterone.
  • 27. Estrogen levels  Step-10: A transitory drop in the level of circulating estrogen occurs at midcycle.  The estrogen-secreting follicle meets its demise at ovulation.  The estrogen level climbs again during the luteal phase because of the CL’s activity, although it does not reach the same peak as during the follicular phase.  What happen if it reach peak?
  • 28. Luteal phase  LH surge  Moderate levels of estrogen – negative feedback  High levels of estrogen – positive feedback and LH surge  Step-17: Progesterone, which dominates the luteal phase, powerfully inhibits LH secretion as well as FSH secretion by acting at both the hypothalamic ARC nucleus and the anterior pituitary.  Furthermore, the luteal cells secrete inhibin, which selectively inhibits FSH secretion.
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  • 31. Luteal phase  Why it is important to inhibit FSH and LH in luteal phase???
  • 32. Luteal phase  If not inhibited there may be maturation and ovulation of another follicle in luteal phase.
  • 33. Luteal phase  Step-18: The corpus luteum functions for an average of 2 weeks and then degenerates if fertilization does not occur.  The mechanisms that govern degeneration of the CL are not fully understood.  May be due to fall in LH  Demise of the CL terminates the luteal phase and sets the stage for a new follicular phase.
  • 34. Luteal phase  As the CL degenerates, plasma progesterone (step 19) and estrogen (step 20) levels fall rapidly because these hormones are no longer being produced.  Withdrawal of the inhibitory effects of these hormones on the hypothalamus allows FSH (step 21) and tonic LH (step 22) secretion to modestly increase again.  New follicular phase begins.
  • 35.