2 - Female Reproductive System Flashcards
What are the major roles o Estradiol and Progesterone in the female reproductive system?
What are roles of Inhibin A and B?
- Act directly on the reproductive tract to regulate its functions
- Feedback on Anterior Pituitary and Hypothalamus that regulate gonadotropin release
- Inhibin A and B which inhibit FSH release by Anterior Pituitary
What is the primary source of estrogens in the non-pregnant adult?
What are the major estrogens?
What forms the basis of pregnancy tests?
The maturing follice
- Estradiol (E2) - Principle ovarian estrogen, most potent
- 99% comes from the ovary
- Estrone (E1) - Weaker than estradiol; formed from estradiol by peripheral conversion via aromatase activity in fat via estrogen conversion of androgens
- Estriol (E3) - Weak androgen; in non-pregnant woman, derived from metabolism of E1/E2;
- Clinical: Measured in pregnancy; the placenta synthesizes high E3
What are the two cell types present in ovarian follicle cells to synthesize estrogen?
What hormones regulate this?
What are their principle secretory products?
Enzymes at each cell?
-
Thecal Cells - Regulated by LH - Androstenedione
- Close proximity to blood vessels;ample supple ofLDL Cholesterol for steroid hormon synthesis
- Site of enzymes for androgen synthesis
- Do NOT possess aromatase activity; can NOT convert andogens to estrogens
- Androstenedione is primary androgen secreted by Thecal Cells
-
Granulosa Cells - Regulated by FSH - E2 Primary Product
- During Follicular Phase of ovarian cycle, granulosa cells have limited access to LDL cholesteol (separated from vascular supply)
- Progesterone production limited during this phase
- Do NOT have 17a-hydroxylase activity, unable to convert Pregnenolone / progesterone to androgens
- Have high levels of aromatase/17B-HSD activity; can convert androgens from thecal cells to estrogens
What reeptors are loacted on thecal cells?
What pathway does thi activate?
LH Receptors induce androgen biosynthesis
Activate cAMP Signaling pathways within cell
What receptors are located on Granulosa cells?
What pathway is activated?
FSH recptors activate aromatase activity
Activate cAMP signaling pathway
What is promoted by progestins?
What are the major progestins?
What is the principle source of progesterone in the non-pregnant adult?
- Progestins are steroids that promote gestation
- The major progestins are:
- Progesterone (most potent!)
- 17a-hydroxyprogesterone
- The principle source of progesterone in the non-pregnant adult is the corpus luteum
What is the principle circulating androgen in women?
What is its source?
What are other circulating androgens?
The principle circulating androgen in women is testosterone
Half is derived from peripheral conversion of steroid precursors
Half is produced by ovaries and adrenals
Other circulating androgens: Dihydrotestosterone, Androstenedione, DHEA, DHEA-sulfate
***Reproductive Cycle in Non-Pregnant Women***
Follicular Phase
Ovulatory Phase
Luteal Phase
- Follicular Phase
- Begins w/onset of menstrual bleeding
- Variable in length
- Corresponds to proliferative phase of endometrial cycle
- Ovulatory Phase (~36 hrs)
- Luteal Phase
- Constant Length (13-14 days)
- Corresponds to secretory phase of endometrial cycle
- Ends with onset of next menses
What is developing during the follicular phase?
What is the primary hormone?
What does it correspond to in the endometrial cycle?
- During the follicular phase the preovulatory follicle develops within the ovary
- Estradiol is primary hormone
- Corresponds to Menstrual / Proliferative phases of endometrial cycle
What does the ovulatory phase culminate in?
What are the primary hormones of the Luteal Phase?
What phase of the endometrial cycle correspond to?
What does it end with?
Ovulation
During the Luteal Phase, the Corpus Luteum secretes Progesterone/Estradiol
Luteal Phase corresponds to the secretory phase of th endometrial cycle
Ends with onset of next menses
What is the functional unit of the ovary?
What are its main actions (4)
The follicle is the functional unit of the ovary
- Sustains the oocyte
- Produces hormones to regulate reproductive function
- Spot of endocrine regulation to regulate hormone production and promote ovulation
- Differentiates into endocrine structure, Corpus Luteum after ovulation is complete
What are Primordial Follicles?
What type of junctions are formed?
What is the blood supply?
What stage of division is the oocyte arrested in?
Primary Oocyte surrounded by a single layer of poorly differentiated pregranulosa cells
Pregranulosa Cells form Gap Junctions with each other and the oocyte
The primordial follicle has no independent blood supply
Meiosis I - Prophase
When does primordial follicle formation begin?
What is their status for the duration of a woman’s life?
In the fetus, complete by 6 months old
Primordial Follicles remain dormant in the ovary until recruited to resume growth and development
What occurs in the ovaries in the absence of gonadotropin?
What is the main signaling mechanism for this?
What is the status before puberty?
Growth of Primordial Follicles, involves intraovarian signaling
Prior to puberty, follicular growth occurs but the process is arrested in an early stage of development, and the follicle undergoes atresia
At what stage does a primordial follicle become a primary follicle?
Formation of the Zona Pellucida; as the granulosa cells become cuboidal and begin to undergo mitosis.
Oocyte and granulosa cells increase in size.
What is the next stage of development for primary follicles?
What is this next stage surrounded by?
What surrounds this layer, and what induces its formation?
Growth of primary follicles leads to Preantal Follicles
In Preantral follicles, the oocyte is surrounded by multiple layers of granulosa cells enclosed within the basal lamina.
Surrounding the basal lamina is a thecal layer formed from stromal cells in response to paracrine factors produced by the granulosa cells
What proteins are secreted during the formation of mature preantral follicles?
What type of receptors do granulosa cells begin to express?
- Oocyte grows and secretes the following into the Zona Pellucida:
- ZP1
- ZP2
- ZP3
- These provide species specific binding sites for sperm cells
- Continued secretion of paracrine factors to stimulate:
- growth/differentiation of granulosa cells (causing formation of multilayered structure)
- Formation of thecal layer from stromal cells
- Granulosa cells begin to express FSH and Estrogen Receptors, but still depend on paracrine factors to support growth!
What do follicles release to promotes formation of vascular supply?
What occurs in the granulosa layer wrt vascularization?
Follicles release angiogenesis factors that promote formation of a vascular supply
Granulosa Layer remains avascular until after ovulation
What do early antral follicles become responsive to?
Are they dependent on this?
How does thi change with larger antral follicles?
Early antral follicles become responsive to the growth-promiting effects of Follicle Stimulating Hormone (FSH)
No, considered independent of FSH for survival
Larger antral follicles become highly dependent on FSH for survival
What enhances the steroidogenic capacity of rapidly growing large antal follicles?
What do thecal cells express, and what is their major secretory product?
What does FSH stimulate expression of?
What secretion increases as follicle matures?
Responsiveness to gonadotropins
- Thecal Cells express LH receptors and enzymes for steroidogenesis, major secretory product is androstenedione
- FSH stimulates expression of aromatase in the granulosa cell, enables conversion of androgens to estrogens
- The gonadotropin sensitive thecal and granulosa compartments of follicle form functional unit capable of estrogen production in response to LH / FSH; as follicle matures the capacity to secrete estrogens increases
What populations of cells emerge from granulosa cells? (2x)
What becomes the corpus luteum?
What facilitates capture of oocyte by fallopian tubes?
Mural Cells: close contact with Thecal Layer, actively engaged in steroidgenesis; retained after ovulation, differentiate into corpus luteum
Cumulus Cells: Surround oocute; inner cells maintain gap junctions with oocyte; released with oocyte during ovulation and facilitate capture of oocyte by ciliated fallopian tubes
What is mainly affected by Atresia?
What is fate of Thecal Cells?
What opposes apoptosis of the follice?
What factors promote atresia?
Oocytes / Granulosa Cells
Thecal cells dedifferentiate and return to pool of stromal interstitial cells
FSH opposes apoptosis of the follice
TNFa, Androgens, IL-6 all promote atresia
