58: Female Reproduction Endocrinology Flashcards
This cyclical process of the Ovarian cycle involves growth and maturation of a primordial follicle during the ______ phase (____ and rising estradiol), rupture of a mature Graafian follicle and oocyte discharge during the ______ phase at mid-cycle (____ surge), and conversion of the ruptured follicle to a corpus luteum during the ______ phase (____, high progesterone plus some estradiol). Primordial follicle contains _____ & it discharges the _____.
Progesterone—pro _____ it promotes _______. Progesterone receptor antagonists cause _______. Progesterone levels prepare for growth of ______.
This cyclical process of the Ovarian cycle involves growth and maturation of a primordial follicle during the follicular phase (FSH and rising estradiol), rupture of a mature Graafian follicle and oocyte discharge during the ovulatory phase at mid-cycle (LH surge), and conversion of the ruptured follicle to a corpus luteum during the luteal phase (LH, high progesterone plus some estradiol). Primordial follicle contains ovum & it discharges the ovum.
Progesterone—pro gestation it promotes gestation. Progesterone receptor antagonists cause abortion. Progesterone levels prepare for growth of blastocyst.
Degeneration of the corpus luteum to form a corpus _____ proceeds if fertilization _____ occur (_____ estrogen and progesterone).
Degeneration of the corpus luteum to form a corpus albicans proceeds if fertilization does not occur (low estrogen and progesterone).
What is a corpus luteum?
The corpus luteum develops from an ovarian follicle during the luteal phase of the menstrual cycle or estrous cycle, following the release of a secondary oocyte from the follicle during ovulation.
The corpus luteum (Latin for “yellow body”) is a temporary endocrine structure in female mammals that is involved in the production of relatively high levels of progesterone and moderate levels of estradiol and inhibin A. It secretes a moderate amount of estrogen to inhibit further release of gonadotropin-releasing hormone (GnRH) and thus secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). A new corpus luteum develops with each menstrual cycle.
Until puberty, the ovary contains numerous _____ follicles that remain in a dormant state. After puberty, several follicles begin ripening with each _____ cycle. Only _____ follicle becomes a mature follicle; the others ultimately regress. After ovulation and release of the ovum, the mature follicle involutes to form the ______, which persists to the end of the cycle. Primordial follicles are are produced from _____, which is complete by 6 months of age.
Until puberty, the ovary contains numerous primordial follicles that remain in a dormant state. After puberty, several follicles begin ripening with each menstrual cycle. Only one follicle becomes a mature follicle; the others ultimately regress. After ovulation and release of the ovum, the mature follicle involutes to form the corpus luteum, which persists to the end of the cycle. Primordial follicles are are produced from primary oocytes, which is complete by 6 months of age.
______ is the predominant estrogen during reproductive years. _____ in the follicular phase promotes proliferation of the endometrium and primes the uterus for progesterone’s actions. Estrogen primes the uterus for progesterone by increasing the number of progesterone ____ in the uterus.
Estradiol is the predominant estrogen during reproductive years. Estradiol in the follicular phase promotes proliferation of the endometrium and primes the uterus for progesterone’s actions. Estrogen primes the uterus for progesterone by increasing the number of progesterone receptors in the uterus.
_____ from the luteal phase converts the proliferative uterus to a secretory uterus.
Progesterone from the luteal phase converts the proliferative uterus to a secretory uterus.
The thickness of the endometrium increases during the ______ phase. This phase is dominated by _____ and is variable in length (ave ~14 days in a standard 28 day cycle), thus accounting for the observed range of menstrual cycle lengths.
The ______ phase is dominated by _____ and has a fixed length of 14 days following ovulation. _____ promotes accumulation of glycogen, increased glandular secretions, and increased vascularity.
The _____ phase is associated with prostaglandin-mediated vasoconstriction of spiral arteries and local ischemic injury/inflammation. This phase is associated with regression of the corpus luteum.
The thickness of the endometrium increases during the proliferative phase. The proliferative phase is dominated by estrogens and is variable in length (ave ~14 days in a standard 28 day cycle), thus accounting for the observed range of menstrual cycle lengths.
The secretory phase is dominated by progesterone and has a fixed length of 14 days following ovulation. Progesterone promotes accumulation of glycogen, increased glandular secretions, and increased vascularity.
The menstrual phase is associated with prostaglandin-mediated vasoconstriction of spiral arteries and local ischemic injury/inflammation. This phase is associated with regression of the corpus luteum.
Hormonal Regulation of the Menstrual Cycle: The hypothalamic-pituitary-ovarian axis is characterized by both positive and negative feedback over the course of a menstrual cycle.
Initially, _____ stimulates release of LH and FSH by the pituitary. ____ synthesized by developing ovarian follicles has negative feedback effects on the axis. In the luteal phase, the system is characterized by negative feedback: Estradiol, progesterone, and inhibin produced by the _____ have negative feedback actions on gonadotropin (FSH & LH) release.
However, in the _____ _____ phase blood estradiol reaches a high level that initiates positive feedback and a surge in ____ & _____ release, provoking ovulation.
Progesterone, inhibin, & even estrogen rise in ______ phase while FSH & LH decrease. Progesterone is main player in _____ phase. All of these hormones are quiet in the follicular phase.
Pulsatile release of GnRH and pulsatile secretion of LH: High circulating ______ during the late follicular phase “sensitize” the anterior pituitary gonadotrophs to stimulation by GnRH, thereby producing the mid-cycle “surge” in LH (and FSH) release that is necessary for rupture of the growing follicle and ovulation.
Hormonal Regulation of the Menstrual Cycle: The hypothalamic-pituitary-ovarian axis is characterized by both positive and negative feedback over the course of a menstrual cycle.
Initially, GnRH stimulates release of LH and FSH by the pituitary. Estrogen synthesized by developing ovarian follicles has negative feedback effects on the axis. In the luteal phase, the system is characterized by negative feedback: Estradiol, progesterone, and inhibin produced by the corpus luteum have negative feedback actions on gonadotropin (FSH & LH) release.
However, in the late follicular phase blood estradiol reaches a high level that initiates positive feedback and a surge in LH and FSH release, provoking ovulation (note that LH is only necessary for ovulation).
Progesterone, inhibin, & even estrogen rise in luteal phase while FSH & LH decrease. Progesterone is main player in luteal phase. All of these hormones are quiet in the follicular phase.
Pulsatile release of GnRH and pulsatile secretion of LH: High circulating estrogens (estradiol) during the late follicular phase “sensitize” the anterior pituitary gonadotrophs to stimulation by GnRH, thereby producing the mid-cycle “surge” in LH (and FSH) release that is necessary for rupture of the growing follicle and ovulation.
The hypothalamic-pituitary-ovarian axis:
Small-bodied neurons in the arcuate nucleus and the preoptic area of the hypothalamus secrete _____, a decapeptide that reaches the gonadotrophs in the anterior pituitary via the long portal veins, to increase secretion and synthesis of FSH (primarily during the follicular phase) & LH (primarily during the luteal phase).
Gonadotropin secretion: GnRH binds to a _____ on the gonadotroph membrane, triggering the _____ signaling pathway. Stimulation causes the gonadotrophs to synthesize and release two gonadotropins: FSH & LH that are stored in secretory granules. Both FSH and LH are ___protein heterodimers comprised of common a-subunits and unique B-subunits.
FSH binds to receptors on ______ cells, stimulating gene transcription and synthesis of relevant enzymes (e.g., aromatase), activins, and inhibins. LH binds to receptors on ovarian _____ cells, stimulating the biosynthesis of progestins and androgens. The androgens enter granulosa cells, where they are converted to estrogens.
Negative feedback on the hypothalamic-pituitary- ovarian axis occurs by several routes. The activins and inhibins act only on the _____. However, the estrogens and progestins act on both the ____ and _____ neurons, exerting both positive and negative feedback controls.
The hypothalamic-pituitary-ovarian axis:
Small-bodied neurons in the arcuate nucleus and the preoptic area of the hypothalamus secrete GnRH, a decapeptide that reaches the gonadotrophs in the anterior pituitary via the long portal veins, to increase secretion and synthesis of FSH (primarily during the follicular phase) & LH (primarily during the luteal phase).
Gonadotropin secretion: GnRH binds to a G-protein-coupled receptor on the gonadotroph membrane, triggering the IP3/DAG signaling pathway. Stimulation causes the gonadotrophs to synthesize and release two gonadotropins: FSH & LH that are stored in secretory granules. Both FSH and LH are glycoprotein heterodimers comprised of common a-subunits and unique B-subunits.
FSH binds to receptors on granulosa cells, stimulating gene transcription and synthesis of relevant enzymes (e.g., aromatase), activins, and inhibins. LH binds to receptors on ovarian theca cells, stimulating the biosynthesis of progestins and androgens. The androgens enter granulosa cells, where they are converted to estrogens.
Negative feedback on the hypothalamic-pituitary- ovarian axis occurs by several routes. The activins and inhibins act only on the anterior pituitary. However, the estrogens and progestins act on both the anterior pituitary and on hypothalamic neurons, exerting both positive and negative feedback controls.
Ovarian steroid hormones are synthesized from ____, estradiol and progesterone are the primary forms. (e.g., the estrogenic potency of β-estradiol is 10x that of estrone and 80x that of estriol).
In serum, Ovarian steroid hormones bind loosely to albumin & sex hormone-binding globulins (SHBGs). They exert effects on many tissues in the body including the breast, bone, vagina, cervix, fallopian tubes, and uterus.
Estrogens are ______ in the liver through conjugation with glucuronic or sulfuric acids, and excreted in the _____ (and to a lesser extent in bile). Progesterone is rapidly degraded in the _____ to steroids with no progestational effect, and excreted in _____.
The side-chain cleavage enzyme that produces pregnenolone is also known as ______. The ovary differs from the testis in having high amounts of ______, which converts androgens to estrogens. See pg. 12 briefly for the synthesis of androgens.
Ovarian steroid hormones are synthesized from cholesterol, estradiol and progesterone are the primary forms. (e.g., the estrogenic potency of β-estradiol is 10x that of estrone and 80x that of estriol).
In serum, Ovarian steroid hormones bind loosely to albumin & sex hormone-binding globulins (SHBGs). They exert effects on many tissues in the body including the breast, bone, vagina, cervix, fallopian tubes, and uterus.
Estrogens are inactivated in the liver through conjugation with glucuronic or sulfuric acids, and excreted in the urine (and to a lesser extent in bile). Progesterone is rapidly degraded in the liver to steroids with no progestational effect, and excreted in urine.
The side-chain cleavage enzyme that produces pregnenolone is also known as 20,22 desmolase. The ovary differs from the testis in having high amounts of aromatase, which converts androgens to estrogens. See pg. 12 briefly for the synthesis of androgens.
Two-cell, two-gonadotropin model of steroid synthesis:
During the follicular phase, the major product of the follicle is ______, whereas during the luteal phase, the major products of the corpus luteum are the ______, although estradiol synthesis is still substantial. In the follicular phase, LH primes the ______ cell to convert cholesterol to _______. Because the theca cell lacks ______, it cannot generate estradiol from this androstenedione. Instead, the androstenedione diffuses to the ______ cell, whose aromatase activity has been stimulated by ____. The aromatase converts the androstenedione to estradiol.
In the luteal phase, the vascularization of the corpus luteum makes _____ available to the granulosa-lutein cells. Thus, both the theca-lutein and the granulosa-lutein cells can produce ______, the major product of the corpus luteum. Note that ___ is major cholesterol source for progesterone synthesis.
For production of 17a-hydroxyprogesterone (17a-OH progesterone), some of the progesterone diffuses into the ______ cell, which has the 17a-hydroxylase activity needed for converting the progesterone to 17a-hydroxyprogesterone. The theca-lutein cell can also generate the androstenedione, which diffuses into the granulosa-lutein cell for _____ synthesis.
During the follicular phase, the major product of the follicle is estradiol, whereas during the luteal phase, the major products of the corpus luteum are the progestins, although estradiol synthesis is still substantial. In the follicular phase, LH primes the theca cell to convert cholesterol to androstenedione. Because the theca cell lacks aromatase, it cannot generate estradiol from this androstenedione. Instead, the androstenedione diffuses to the granulosa cell, whose aromatase activity has been stimulated by FSH. The aromatase converts the androstenedione to estradiol.
In the luteal phase, the vascularization of the corpus luteum makes LDL available to the granulosa-lutein cells. Thus, both the theca-lutein and the granulosa-lutein cells can produce progesterone, the major product of the corpus luteum. Note that LDL is major cholesterol source for progesterone synthesis
For production of 17a-hydroxyprogesterone (17a-OH progesterone), some of the progesterone diffuses into the theca-lutein cell, which has the 17a-hydroxylase activity needed for converting the progesterone to 17a-hydroxyprogesterone. The theca-lutein cell can also generate the androstenedione, which diffuses into the granulosa-lutein cell for estradiol synthesis.
Estrogens have diverse effects including:
- _____ of the uterine endometrial stroma & development of endometrial glands
- _____ & development of mucosal lining of the fallopian tubes
- _____ of bone growth by inhibition of osteoclastic activity
- Increased _____ deposition in subcutaneous tissues
Progesterone has diverse effects including:
- _____ changes in the uterine endometrium (of major importance)
- _____ frequency & intensity of uterine contractions
- _____ fallopian tube secretions
Estrogens have diverse effects including:
- proliferation of the uterine endometrial stroma & development of endometrial glands
- Proliferation & development of mucosal lining of the fallopian tubes
- Stimulation of bone growth by inhibition of osteoclastic activity
- Increased fat deposition in subcutaneous tissues
Progesterone has diverse effects including:
- Secretory changes in the uterine endometrium (of major importance)
- Decreased frequency & intensity of uterine contractions
- Increased fallopian tube secretions
Menstrual Cycle:
During the female menstrual cycle, changes take place in the ovaries and uterus, under the control of the hypothalamus and anterior pituitary gland.
During the _____ phase, several primary follicles undergo further development in response to _____ and synthesize androgens, which are converted to _____ under the influence of _____. Ultimately, one follicle fully matures and the others regress. The uterine endometrium proliferates in response to ______. Primary follicle is “chosen” & it makes _____, the rest degenerate. Theca cells are on the ____ & granulosa cells are on the ____ of the follicle.
Near midcyle, estradiol rises to a level that initiates positive feedback, and thus a surge in ____ & _____ release by the anterior pituitary, which results in ovulation. During the ensuing luteal phase, the mature follicle becomes the corpus luteum, which secretes _____ and _____. The uterus undergoes further proliferative and secretory changes. Estrogen (Estradiol) made from the Grafian follicle upregulates gnrh _____ in the late follicular phase on the hypothalamus which causes the LH spike. This is the basis of the LH surge.
Unless pregnancy occurs, endometrial sloughing and menstruation eventually occur, marking the beginning of a ___ cycle.
There is an _____ in basal body temperature following ovulation, and due to progesterone effects on the hypothalamus. Girl gets into “heat”.
Menstrual Cycle:
During the female menstrual cycle, changes take place in the ovaries and uterus, under the control of the hypothalamus and anterior pituitary gland.
During the follicular phase, several primary follicles undergo further development in response to FSH and synthesize androgens, which are converted to estradiol under the influence of LH. Ultimately, one follicle fully matures and the others regress. The uterine endometrium proliferates in response to estradiol. Primary follicle is “chosen” & it makes estradiol, the rest degenerate. Theca cells are on the outside & granulosa cells are on the inside of the follicle.
Near midcyle, estradiol rises to a level that initiates positive feedback, and thus a surge in LH and FSH release by the anterior pituitary, which results in ovulation. During the ensuing luteal phase, the mature follicle becomes the corpus luteum, which secretes progesterone and estradiol. The uterus undergoes further proliferative and secretory changes. Estrogen (Estradiol) made from the Grafian follicle upregulates gnrh receptors in the late follicular phase on the hypothalamus which causes the LH spike. This is the basis of the LH surge.
Unless pregnancy occurs, endometrial sloughing and menstruation eventually occur, marking the beginning of a new cycle.
There is an increase in basal body temperature following ovulation, and due to progesterone effects on the hypothalamus. Girl gets into “heat”.
Puberty: the transition to ____ female reproductive function
Thelarche: ____ development
Adrenarche: increased secretion of _____ ______
Menarche: menstrual cycle _______
Puberty: the transition to cyclic female reproductive function
Thelarche: breast development–tetas
Adrenarche: increased secretion of adrenal androgens
Menarche: menstrual cycle begins
Estrogens:
- inhibit ______ in bone, promoting rapid growth, followed by uniting of epiphysis with shafts of long bones to stop growth
- Promote deposition of _____, development of stromal tissue and ductile growth in _____
- Promote deposition of fat in _____ tissue
Progesterone:
-Promotes development of lobules & alveoli in ______
Estrogens:
- inhibit osteoclasts in bone, promoting rapid growth, followed by uniting of epiphysis with shafts of long bones to stop growth
- Promote deposition of fat, development of stromal tissue and ductile growth in breasts
- Promote deposition of fat in subcutaneous tissue
Progesterone:
-Promotes development of lobules & alveoli in breasts
