Female GT and Breast Flashcards
fundamental reproductive unit of FGT
- ovarian follicle
- composed one one germ cell surrounded by endocrine cells
menarche
- beginning of menstrual cycle
- average age 11-13
female monthly sexual cycle
- controlled by gonadotropins
- only single ovum released
- endometrium is prepped for implantation
ovarian cycle
- follicular phase- 15 d
- ovulatory phase- ends with ovulation
- luteal phase- 13d
female hormonal system
- GnRH from hypothalamus
- FSH and LH from pituitary
- estrogen and progesterone from ovaries
what is the predominating hormone during the follicular phase
- estrogen
- low levels of FSH, LH and progesterone
what happens around day 14
- LH surge
- ovulation occurs
what is the predominating hormone during the luteal phase
- progesterone that is released by corpus luteum
oogenesis
- germ cells in ovary differentiate to oogonia
- divide by mitosis
- mature into primary oocytes
- enclosed in primordial follicles
what happens at puberty
- periodic secretions of FSH triggers meiosis
- only one completes meiosis I
- produces polar bodies and secondary oocytes
when is meiosis II completed
after fertilization of ovum by sperm
cells of the follicle
- theca cells= outer portion
- granulosa cells= inner portion that provide nourishment
estrogen
- steroid hormone
- comes from androgenic precursors
- transformed by aromatase from testosterone to estrogen
- have E1-3
E1
- predominant estrogen after menopause
E2
- produced in theca and granulosa cells
- predominant estrogen in premenopausal women
E3
estrogen of the placenta during pregnancy
types of estrogen receptors
- ER alpha
- ER beta
- GPER (g-protein coupled estrogen receptor)
ER alpha
- predominant in uterus, mammary glands, and may places throughout body
- sustained exposure to estrogen and activation of ER alpha -> cancer of breast and endometrium
ER beta
- predominantly expressed in ovaries and prostate
- activates anti-proliferative and pro-apoptotic pathways in cancers
GPER
- mediates rapid estrogen signaling by stim adenylyl cyclase
- expressed in normal ovary
- regulates physiological processes like follicle maturation
clinical disorders associated with estrogen
- endometriosis
- fibroids
- PCOS
endometriosis
- chronic hormone dependent inflammatory disease
- growth of endometrial tissue outside uterus
- pathogenesis is multifactorial
clinical sx of endometriosis
- moderate to severe pain
- dysmenorrhea
- low back pain
- infertility
most common anatomic site for endometriosis
- ovaries*
- anterior and posterior cul de sac
- broad ligaments
Sampson’s theory of retrograde menstruation
- during menses
- endometrial cells flow backwards through fallopian tubes into peritoneal cavity
- results in endometriosis
pre-menarcheal endometriosis
- undifferentiated cells of mullerian origin in peritoneal cavity differentiate into endometrial tissue
- results in endometriosis
major causes of endometriotic pain
- endometriotic lesions -> stimulate nociceptors
- innate immune system -> NGF
- peripheral NS
uterine leiomyomas
- aka fibroids
- benign tumors of myometrium
- most common pelvic tumor
leiomyoma significance
- effects function and structure of endometrium
- causes excessive bleeding in uterus
leiomyoma pathogenesis
- genetics- trisomy 12 and point mutations
- Steroid hormones cause mitogenic stimuli
- increased vascularity and venular ectasia
- fibrotic factors
polycystic ovarian syndrome (PCOS)
- intraovarian androgen excess
- closely associated with insulin resistance
- predisposes pts to metabolic dysfunction and type 2 DM
presentation of PCOS
- hirsutism
- menstrual irregularities
- infertility due to infrequent or absent ovulation
PCOS etiology
- first hit- inherited predisposition
- second hit- postnatal provocative hit
- second hit is usually insulin resistant hyperinsulinemia
steroidogenesis and PCOS
- down regulation of thecal androgen production is flawed
- hyper-responsive to LH
- excess androgen -> anovulation and polycystic ovaries
summary of issues in PCOS
- ovarian hyperandrogenism
- insulin resistant hyperinsulinemia
- LH excess
- obesity
premenstrual syndrome (PMS)
- physical and/or behavioral sx in second half of menstrual cycle
- abdominal bloating
- breast tenderness
- HA
pathogenesis of PMS
- normal serum estrogen or progesterone
- abnormal neurotransmitter response to hormonal changes
- assoc with low serotonin
what is the more severe version of PMS?
Premenstrual dysphoric disorder (PMDD)
processes that contribute to menopause
- hypothalamic and ovarian aging
- environmental, genetic, and lifestyle factors
- systemic diseases
result of hypothalamic aging
- desynchronized GnRH production
- impaired LH surge
what are the two major structures of the breast
- ducts
- lobules
what are the two types of epithelial cells
- luminal
- myoepithelial
breast structural changes in 1st half of menstrual cycle
- lobules are quiescent
breast structural changes after ovulation
- cell proliferation and number of acini per lobule increases
- intralobular stroma becomes edematous
breast structural changes on menstruation
- regression of lobules and disappearance of edema
breast tissue at puberty
- estrogen and progesterone induces branching of ductal sys and dev of lobules
breast tissue during pregnancy
- progesterone and prolactin high
- permanent increase in number/size of lobules
- oxytocin -> proliferation
- after lactation, apoptosis of epithelium and lobule atrophy
breast tissue during aging and menopause
- atrophy
- decrease in CT
- increase in adipose
cancers of lobule and terminal ducts
carcinoma
cancers of intralobular stroma
fibroadenoma
major classifications of benign breast lesions
- non-proliferative
- proliferative without atypia
- atypical hyperplasia
non-proliferative benign breast lesions
- not associated with increased risk of cancer
- simple breast cyst- fluid filled mass
fibroadenomas
- proliferative benign tissue without atypia
- associated with small increased risk of breast cancer
- can be either simple or complex
atypical hyperplasia
- substantial increased risk in developing breast cancer
simple fibroadenomas
- likely hormonal
- contain glandular and fibrous tissue
- no increased risk of breast cancer
complex fibroadenomas
- slight increased risk of breast cancer when multicentric changes present
pathophys of fibroadenomas
- can be stimulated by estrogen, progesterone, and lactation
- some have receptors that respond to epidermal growth factor and growth hormone
- rarely seen in older pts
fibroadenomas in elderly
- increased stromal growth
- necrosis
what is the most common type of breast cancer
- adenocarinoma
- usually ductal
what does HER2 stand for
human epidermal growth factor receptor 2
HER2 oncogene
- encodes HER2 receptors
- type of EGFR receptor
- controls cell growth and differentiation
- possibly controls angiogenesis
major genetic pathways of carcinogenesis
- ER+, HER2-
- HER2+
- ER-, HER2-
ER+, HER2-
- 50-65% of cancers arise from this pathway
HER2 and ER cross-talk
- ER and HER2 are main drivers of cell proliferation and survival in breast caner
- if positive for both must target both pathways
- if you dont target both get a resistance to thearpy
ductal carcinoma in situ (DCIS)
- malignant proliferation of epithelial cells limited to ducts by basement membrane
- nuclear grade and/or presence of necrosis
- low, intermed, or high grade
high grade DCIS
- lacks estrogen and progesterone reeptors
- high proliferative rates
- over expression of HER2, p53 and angiogenesis
low grade DCIS
- estrogen and porgesterone positive
- low proliferative rate
- rarely show abnormalities in HER2 or p53
ER+ HER2- invasive breast carcinoma
- low proliferatoin
- responds best to hormonal treatment
- incomplete response to chemotherapy
ER+ HER2- invasive breast cancer
- high proliferation
- some respond to chemotherapy
most common familial mutations in breast cancer
- BRCA1 and BRCA2
- tumor suppressor proteins that normally repair DNA damage
sporadic breast cancer
- major risk factor= hormone exposure
- age of menarche and menopause
- reproductive history
- breastfeeding
- exogenous estrogens
- radiation exposure
