Estrogens

Question 1

what type of hormone is estrogen

Answer 1

*a STEROID hormone

Question 2

estrogen - functions

Answer 2

1. developing and maintaining the female reproductive tract (uterus, fallopian tubes, cervix, vagina)
2. developing and maintaining female secondary sex characteristics (breast development, fat distribution)
3. inducing progesterone receptors in the uterus, breast, and brain
4. preparing for / maintaining pregnancy and lactation (maintaining endometrial proliferation, breast ductal system)
5. increasing HDL and decreasing LDL cholesterol (lower estrogen in menopause → increased risk of atherosclerosis)
6. increasing bone mass (lower estrogen in menopause → increased risk of fractures)
7. fusing growth plates

Question 3

estrogen - 3 types

Answer 3

1. estradiol: most potent estrogen; made in maturing follicles
2. estrone: most prevalent in post-menopausal females; made from aromatase enzyme in adipose tissue; important for bone health after menopause
3. estriol: most prevalent in pregnant females; least potent

Question 4

estradiol - overview

Answer 4

*most potent estrogen
*made in maturing follicles
*aka 17 beta estradiol or E2

Question 5

estrone - overview

Answer 5

*most prevalent in post-menopausal females
*made from aromatase enzyme in adipose tissue
*important for bone health after menopause

Question 6

estriol - overview

Answer 6

*most prevalent in pregnant females
*least potent

Question 7

estrogen production

Answer 7

*main source of circulating estrogens in ovulating females is from ovarian follicles
*a follicle during the pre-ovulatory phase of the menstrual cycle:
-theca cells produce androgens (androstenedione, testosterone) from pregnenolone in several steps
-granulosa cells produce estradiol from androgens made by the theca cells; they also produce progesterone

Question 8

estrogen synthesis

Answer 8

*LH binds to theca cell GPCRs → promotes androgen production; androgens diffuse to granulosa cells
*FSH binds to granulosa cell receptors → promotes aromatase expression → conversion of androgens to estrogens

Question 9

progesterone - overview

Answer 9

*a steroid hormone
*several actions:
1. prepares uterus for pregnancy and breasts for lactation:
-induces differentiation of the endometrium into secretory endometrium required for implantation
-maintains uterine endometrium in pregnancy
2. breast development (induces fat cell growth / division and alveolar-lobular development)
3. increases body temperature by affecting hypothalamic thermoregulatory center of the brain
4. can be converted to estrogen

Question 10

progesterone synthesis

Answer 10

*during the menstrual cycle, after a follicle ruptures and releases an egg, theca and granulosa cells remaining in the ovary transform into luteal cells, then forms the corpus luteum which secretes progesterone
*without implantation of the fertilized egg, the corpus luteum degenerates and progesterone levels decrease

Question 11

hypothalamic-pituitary-ovarian axis

Answer 11

*pulsatile release of GnRH from hypothalamus → stimulates pituitary to release LH and FSH
1. FSH stimulates follicle development and estradiol production
2. LH: midcycle LH surge causes ovulation; LH maintains the corpus luteum and stimulates progesterone and estradiol production

Question 12

negative feedback from oral contraceptive pills

Answer 12

*OCPs contain estrogen & progesterone → negative feedback to the hypothalamus → decreased GnRH → decreased LH and FSH

Question 13

estrogen & progesterone - transport and metabolism

Answer 13

*estrogen and progesterone are steroid hormones derived from cholesterol (lipophilic, hydrophobic)
*transport: bind to sex hormone binding globulin (SHBG) and albumin to travel through the blood
*dissociate from binding proteins, diffuse through cell membrane, and bind intracellular receptor to exert effect by altering gene expression
*metabolism: conjugated with sulfates/glucuronides in the liver and cleared by kidney

Question 14

changes in estrogen levels throughout the life cycle

Answer 14

*childhood: low gonadotropin (LH/FSH) levels
*puberty: onset of pulsatile GnRH and gonadotropin release first during sleep, then more often → estradiol production and secondary sex characteristics
*menopause: high gonadotropin levels (FSH/LH)

Question 15

menopause hormones

Answer 15

*loss of ovarian estrogen production results in lack of negative feedback to pituitary and absence of inhibin production
1. FSH increases (due to absence of inhibin from developing follicles)
2. LH increases (due to lower estrogen levels)
3. the adrenal glands can make weak androgens which can be converted to estrogen in adipose tissue

Question 16

symptoms of menopause (aka “menopausal syndrome”)

Answer 16

*hot flashes
*night sweats
*mood changes
*headaches
*sleep disturbances
*loss of libido
*memory loss
*atrophy of vaginal epithelium
*changes in vaginal pH
*decrease in vaginal secretions
*reduced blood flow to uterus and vagina
*pelvic relaxation, incontinence
*osteoporosis
*cardiovascular disease

Question 17

menopause - treatment

Answer 17

*goal = relief of symptoms
1. vaginal estrogen cream/lubricants for vaginal dryness
2. hormone replacement therapy (HRT): estrogen
-add progesterone is uterus is present to prevent unopposed endometrium proliferation → endometrial cancer
-contraindicated if history of breast cancer, blood clots, stroke
3. if unable to do HRT, can try SSRI, SNRI for vasomotor symptoms

Question 18

effects of exogenous estrogen (hormone replacement therapy, OCPs) on thyroid

Answer 18

*increases hepatic synthesis of thyroid binding globulin leading to increased total (bound) T3/T4 levels
*free T4, free T3, and TSH are unaffected and patient does not have thyroid synthesis
*overall: increased TBG and total T3/T4; NORMAL free T4/T3

Question 19

estrogen/progesterone levels in pregnancy

Answer 19

*hCG can be detected in urine after a missed menstrual period (pregnancy test = hCG antibodies)
*first trimester: hormone production from corpus luteum (estrogen, progesterone) is now under regulation of hCG (similar in structure to LH, but more potent)
*second/third trimester: placenta and fetus mature sufficiently to produce estriol and progesterone independently of corpus luteum

Question 20

placental hormones

Answer 20

*hCG stimulates estrogen, progesterone, and relaxin synthesis
1. estrogen: increases growth/development of myometrium, placenta, mammary glands; increases prolactin secretion from pituitary for breast development
2. progesterone: stimulates placental growth, decreases myometrial contractions, stimulates mammary gland development, acts as a precursor to other steroids
3 other hormones produced by placenta:
-human placental lactogen (hPL): increases insulin resistance and lipolysis in mother to ensure fetal nutrition

Question 21

human placental lactogen (hPL)

Answer 21

*increases insulin resistance and lipolysis in mother to ensure fetal nutrition
*hPL is a big contributor to development of gestational diabetes
*after delivery of placenta, hPL levels drop significantly and women have a decrease in insulin resistance