Endocrine 2 Exam 1: Estrogens, Progestins (p1-10)

What 2 hormones does GnRH (gonadotropic releasing hormone) stimulate?

FSH, LH

GnRH binds to its receptor where?

anterior pituitary gland

when GnRH binds to its receptor in the anterior pituitary gland, there is an activation of G-protein (___), which causes activation of _____, which increases ___ and ___

Gq11, PLC, IP3, Ca2+

FSH and LH bind to their receptors where?

ovaries (or testes)

binding of FSH to its receptor in the ovaries results in release of what hormone?

estrogen

binding of LH to its receptor in the ovaries results in release of what hormone?

progesterone

In males, activation of FSH and LH receptors in the testes results in ____ (formation of sperm) and ____ (the synthesis of testosterone)

spermatogenesis, steroidogenesis

In females, activation of FSH receptors also stimulates the ___ of the developing ovarian follicle and induces the expression of ___ receptors on both theca and granulosa cells

growth, LH

FSH also stimulates production of ____ via activation of Gs/AC, which thereby stimulates the production of ___-__ ____

aromatase, 17-β estradiol

Aromatase is found in (5):

fat, ovary, bone, adrenal gland, breast tissue

How is estrogen secreted?

-the adrenal gland releases adrenal androgens (specifically ____), which is converted into estrogens (E1, E2, and E3)

androstenedione

What is E1?

estrone

What is E2?

17-β estradiol

What is E3?

estriol

What receptor does E1 (estrone) bind to?

ESR1

What receptor does E2 (17-β estradiol) bind to?

ESR1 and ESR2

What receptor does E3 (estriol) bind to?

ESR2

ESR1 causes stimulation or inhibition in body?

stimulation

ESR2 causes stimulation or inhibition in body?

inhibition

Following activation of FSH receptors, estrogen is released into _____ and causes its effects by binding to _____ _____ located in the ___ of ____, which ____ to stabilize one another

bloodstream, estrogen receptors, nucleus, cells, dimerize

Estrogen is released into the bloodstream and binds to estrogen receptors, which bind to _____ _____ _____ (___) upstream of ____ to regulate _____ _____.

estrogen response elements, EREs, DNA, gene transcription

Estrogens activate genes involved in:

1) _____ ____ (endometrial lining)

2) breast ____/_____

uterine regeneration, maturation/lactation

Estrogens activate genes involved in:

3) bone protection via ____ of ____ (____ ____)

inhibition, osteoclasts, bone breakdown

remember

_____: breaks bone down :(

______: builds bone :)

osteoclasts, osteoblasts

Estrogens activate genes involved in:

4) the liver- which will generally have ___ effects on HDL/LDL (high HDL, low LDL) but also ____ ___ _____ (so patient has a ____ clot risk)

favorable, increase clotting proteins, higher

Estrogens activate genes involved in:

5) the gallbladder- _____ _____ _____ and ____ _____ _____ (helps emulsify fats to absorb more through GI), and ____ _____ _____

increase cholesterol synthesis, bile salt formation, decrease gallbladder motility

Estrogens activate genes involved in:

5) the brain- _____ ____ _____ ____ and _____ ____

increase cerebral blood flow, body temperature

when LH binds to its receptor:

-acts on the ___ ____ to _____ the dominant _____ during ovulation

-synthesizes ______ by acting on the ___ ___

theca cells, rupture, follicle, progesterone, corpus luteum

corpus luteum: the portion of the ovum that remains following the ___ of ____ during _______

bursting, egg, ovulation

LH also helps to regulate ___ ___ expression

FSH receptor

Progesterone is released into the ______ and binds to the ______ ______, which then binds to ____ _____ ____ (____) upstream of ____ to regulate _______ ______

bloodstream, progesterone receptor, progesterone response elements, PREs, DNA, gene regulation

Progesterone activates genes involved in:

1) _____ ____ (most _____ w/ _____)

2) breast ___/____

uterine protection, estrogen, progesterone, maturation/lactation

Progesterone activates genes involved in:

3) bone protection via ____ of ____

stimulation, osteoblasts

Progesterone activates genes involved in:

4) the liver- which will generally have ___ effects (increase LDL) but also ___ _____ ____(so patient has a ___ clot risk)

unfavorable, increase clotting proteins, higher

Progesterone activates genes involved in:

5) the gallbladder- _____ ____ (affecting absorption of _____ in body)

decrease motility, cholesterol

Progesterone activates genes involved in:

5) the brain- _____ _____ _____ ____ and ____ ____

increase cerebral blood flow, body temperature

ESR1 is located on the _____ ___ ___ which consists of (10):

female reproductive tract, uterus, vagina, ovary, mammary tissue, vascular smooth muscle, bone, liver, gall bladder, hypothalamus, anterior pituitary gland

where ESR1 is located, feedback inhibition is located on (2):

hypothalamus, anterior pituitary gland

are the following homodimers or heterodimers?

ESR1: ESR1: _____

ESR2: ESR2: ____

ESR1: ESR2: _____

homodimer, homodimer, heterodimer

when ESR1 binds with ESR1, this forms a homodimer with a ___ response on ____ ____ ____

stimulatory, ERE-mediated gene transcription

when ESR2 binds with ESR2, this forms a homodimer with an ___ response on _____ _____ ____

inhibitory, ERE-mediated gene transcription

when ESR1 binds with ESR2, this forms a heterodimer that has ___ stimulatory/inhibitory action dependent on the amount of ESR1:ESR2

mixed

E1 (estrone) has a 5:1 selectivity for ESR1:ESR2, so it will primarily have stimulatory or inhibitory action?

stimulatory

E2 (17-β estradiol) has a 1:1 selectivity for ESR1:ESR2, so it will primarily have stimulatory or inhibitory action?

mixed stimulatory/inhibitory action dependent on amount of ESR1:ESR2

E3 (estriol) has a 1:5 selectivity for ESR1:ESR2, so it will primarily have stimulatory or inhibitory action?

inhibitory

Estrogen receptors are either ___ receptors (ESR1 and ESR2) that directly affect gene transcription, or ______ (_____) _____ ____

genomic, ESR1, ESR2, non-genomic, GPR30, steroid receptor

Both the estrogen receptors (ESR1 and ESR2) and the progesterone receptors (___ and ___) are located in the ___ of the ___

PRA, PRB, nucleus, cell

GPR30 is a cell membrane estrogen receptor that mediates ____ ____

antioxidant signaling

The progesterone receptors, PR-A and PR-B, are ___ ___ from a ___ ___

splice variants, single gene

when PRA binds with PRA, this forms a homodimer with a ___ response on ____ to ____ ____ ____

stimulatory, PRE, increase gene transcription

when PRB binds with PRB, this forms a homodimer with an ___ response on ____ to ___ _____ ______

inhibitory, PRE, decrease gene transcription

when PRA binds with PRB, this forms a heterodimer that has ___ stimulatory/inhibitory action dependent on the amount of PRA:PRB

mixed

Progesterone receptors are located on (7):

uterus, mammary tissue, bone, liver gallbladder, hypothalamus, anterior pituitary gland

Under normal conditions, estrogen/ERs in the uterus cause a _____ of the _____ ____ during days __-__ of the female menstrual cycle

regeneration, endometrial lining, 8-26

During pregnancy, estrogen/ERs in the uterus keep the endometrial lining highly ___ during ____ to provide ___ to the ______ ______

vascularized, gestation, nutrients, developing embryo

In excess, since estrogen/ERs are strong ____ in the ____, using these compounds in the ____ of _______ could cause excessive _____ ___ leading to ______ ___

mitogens, uterus, absence, progesterone, endometrial hyperproliferation, endometrial cancer

mitogens = ____ ___ that trigger cells to start ____

signaling molecules, dividing

Under normal conditions, progesterone in the uterus ____ the _____ ____ induced following _____ ____ during the female menstrual cycle.

maintains, uterus lining, estrogen exposure

Under normal conditions, progesterone in the uterus prevents ____ ____ that could lead to endometrial cancer by ____ _____/___ actions

endometrial hyperproliferation, inhibiting, estrogen/ER’s

Progesterone prevents endometrial hyperproliferation by inhibiting estrogen/ER. This is why it must be used in ___ with ____ in _____ ____ and ____ _____ agents!!

combination estrogen, hormone therapy, oral contraceptive

remember effects on endometrial lining:

estrogen ____

progesterone ____

regenerates, maintains

Upregulation of the PR gene increases PR ___ and PR __ expression

mRNA, protein

Upregulation of the PR gene increases PR mRNA and PR protein expression, enhancing the _____ ____ to _____ (__)

cellular response, progesterone

Upregulation of the PR gene increases PR mRNA and PR protein expression, enhancing the cellular response to P4. Activated PR then ____ _____ ____ (__) binding to _____ (__).

inhibits estrogen receptor, ER, estradiol, E2

During pregnancy, progesterone in the uterus prevents _____ _____ ____ ____ (____) to prevent ____

uterine smooth muscle contraction, myometrium, miscarriage

Under normal conditions, _____/___ and ____ in the breast cause a ____ of the breast tissue during ____

estrogen/ERs, progesterone, maturation, puberty

During pregnancy, estrogen and progesterone prepare the breast for _____ ____ (____)

milk production, lactation

In excess, since estrogen and progesterone are ______, supplementation of these hormones may ____ the risk for ____ ___

mitogenic, increase, breast cancer

Under normal conditions in the bone, estrogen/ERs inhibits _____ (decrease ____ _____) and progesterone stimulates _____ (increase ____ ____)

osteoclasts, bone resorption, osteoblasts, bone formation

Due to their effect in the bone, one of the uses of estrogen (ex. ______) or progesterone following menopause is to prevent ______ ____ following ___ _____ of ______ and ______

raloxifene, postmenopausal osteoporosis, low levels, estrogen, progesterone

Under normal conditions, estrogen/ERs in the liver changes lipid profiles in a ____ manner by ___ HDL and ___ LDL

lipid profiles, favoring, increasing, decreasing

In the liver, a lack of ______ (especially in postmenopausal women) will therefore ___ HDL and ___ LDL

estrogen, decrease, increase

Under normal conditions, progesterone in the liver changes _____ _____ in an _____ manner by ____ LDLs

lipid profiles, unfavorable, increasing

In excess in the liver, progesterone can increase ___ ___ ___ via increasing ____

coronary artery disease, LDL

Under normal conditions in the liver, estrogens (mainly conjugated estrogens, ethinyl estradiol) stimulate ____ ___

liver proteins

Under normal conditions in the liver, progesterone can increase fibrinogen, prothrombin fragment 1.2, D-dimer, plasminogen, plasmin-antiplasmin complex, protein C activity and decrease antithrombin activity, t-PA activity, and PAI activity. Ultimately, this means _____ can increase one's risk of ___ ___

progesterone, blood clots

In excess in the liver, progesterone can lead to an ____ in the formation of (4):

increase, DVT, VTE, PE, TIA

Under normal conditions in the gall bladder, estrogen/ERs increase hepatic transporters:

-ABCG5/G8, increasing __ secretion

-ABC11, increasing __ __ secretion

-ABCB4, increasing ___ secretion

cholesterol, bile salt, phospholipid

Under normal conditions in the gall bladder, estrogen/ERs also stimulate ___ ___ ___ and _____ ______ ____ in the intestine by increasing niemann-pick c1-like protein (____)

HMG coA reductase, increase cholesterol uptake, intestine, increase NPC1C1

Under normal conditions, both estrogen and progesterone ___ ____ of the gall bladder

decrease motility

During pregnancy, in the gall bladder, estrogen and progesterone increase risk of ___ ___ due to increased propensity to form ____ ____ from excess saturation of ____ cholesterol and ____ of gall bladder

gall stones; cholesterol crystals, biliary, hypomotility

In excess, in the gall bladder, estrogen increases ___ ___ ____, increasing risk for ___ ____

cholesterol saturation index, gall stones

In excess, in the gall bladder, both progesterone and estrogen ___ gall bladder ______, increasing risk for gall stones

decrease, motility

In the brain, estrogen/ERs cause changes in cerebral blood flow via _____ ___ ___ production which causes cerebral ____

increasing nitric oxide, vasodilation

In the brain, changes in estrogen leves could cause ____ in premenopausal women

migraines

It is through estrogen receptors in the brain that many of the ___ symptoms (hot flashes, night sweats, flushing, tingling) occur during peri-menopause where estrogen levels are erratic (high then low)

vasomotor

Through activity the brain, progesterone ___ ____ ____ by 1°F and can cause ____

increases body temperature, drowsiness

in the hypothalmic/pituitary axis of the brain, estrogens/ERs and progesterone/PRs cause a ___ in the _____ of ____

decrease, release, GnRH

estrogens/ERs and progesterone/PRs cause a decrease in the release of GnRH, which results in a decrease of both ___ and ___

FSH, LH

estrogens/ERs and progesterone/PRs cause a decrease in the release of GnRH, which results in a decrease of both FSH and LH, thereby decreasing ____ _____/______. This is the mechanism by which _____ _____ prevent _____

egg, formation/ovulation, oral contraception, ovulation

FSH produces __ and LH produces ___

estrogen, progesterone

Formation of estrogen via FSH will cause feedback ___ on ____ _____ to their _____

inhibition, estrogen binding, receptor

Formation of progesterone via LH will cause feedback ___ on _____ _____ to their ______

inhibition, progestin binding, receptor

Progesterone is the natural hormone in the body, whereas ___ are ______ ______ of progesterone that are used clinically.

progestins, synthetic mimics

Estrogen via the estrogen receptor acts on a "______" of proteins that reside in ___ known as the ___ __ ___

complex, DNA, estrogen response element

The ____ _____ (ex. where the dimerized ER binds) for the ERE is (GGTCAnnnTGACC)

consensus sequence

In the absence of _____, proteins are bound to the ____ and ___ _____ ______

estrogen, ERE, prevent gene transcription

In the absence of estrogen, proteins are bound to the ERE and prevent gene transcription. However, when estrogen binds its receptor and the resulting complex ____ with the proteins on the ERE, gene transcription is activated.

interacts

After estrogen binds to its receptor and the receptors dimerize, co-activators (SWI/SNF) and histone acetyltransferase (____) will alter chromatin structure

HAT

histone acetyltransferase (HAT) functions to add ___ groups to lysine residues on histone

acetyl