Estrogen and Progesterone Receptors Overview

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Questions and Answers

What is the primary mechanism of action for estrogen in combined oral contraceptives?

Inhibiting FSH secretion via negative feedback (correct)

Altering endometrial lining

Increasing cervical mucous production

Inhibiting LH secretion

Which of the following is a secondary mechanism of action of progestins in contraceptives?

Altering cervical mucous (correct)

Promoting follicular development

Inhibiting FSH secretion

Enhancing endometrial growth

What is a common side effect of Clomiphene Citrate?

Inhibition of follicular maturation

Elevation of blood pressure

Weight loss

Increased ovulation (correct)

Which of the following formulations of combined oral contraceptives is NOT mentioned?

Quadriphasic Signup and view all the answers

What role do gonadotropins play in the context of fertility?

Induce ovulation through injections of FSH Signup and view all the answers

What is an effect of oral contraceptives on body physiology?

Cervical hypertrophy Signup and view all the answers

Which type of contraceptive is the minipill classified as?

Progestin-only contraceptive Signup and view all the answers

What is the effect of Clomiphene Citrate on estrogen feedback?

Inhibits the negative feedback of estrogen Signup and view all the answers

What does the use of hCG after FSH injections achieve?

Completes follicular maturation and induces ovulation Signup and view all the answers

Which vitamin is known as vitamin B9?

Folic acid Signup and view all the answers

What is a potential result of chronic malnutrition regarding folic acid?

Folic acid deficiency Signup and view all the answers

Which condition could lead to malabsorption affecting folic acid levels?

Chronic liver disease Signup and view all the answers

What is the primary cofactor role of folic acid?

1-carbon transfer reactions Signup and view all the answers

How much folic acid is generally absorbed from an average diet?

50-200 μg Signup and view all the answers

What effect does Doxylamine have in the context of pregnancy?

It acts as an anti-emetic. Signup and view all the answers

Which medication is a first-generation antihistamine used as a sleep-aid during pregnancy?

Doxylamine Signup and view all the answers

What is the mechanism of action for most antipsychotics mentioned?

D2 receptor antagonism Signup and view all the answers

Which statement about chlorpromazine is true?

It was the first widely used antipsychotic. Signup and view all the answers

What happens when estradiol binds to estrogen receptors (ER)?

It forms a homodimer or heterodimer with the receptor. Signup and view all the answers

How do G protein-coupled estrogen receptors (GPCRs) differ from classic estrogen receptors?

They facilitate faster, non-genomic estrogenic activity. Signup and view all the answers

What role does PR-A play in relation to PR-B?

It inhibits the actions of PR-B. Signup and view all the answers

Which physiological effect is associated with estrogen?

Endometrial proliferation. Signup and view all the answers

What occurs when progesterone levels decline at the end of the menstrual cycle?

Menstruation begins. Signup and view all the answers

What is the function of inhibin in the ovaries?

Inhibits FSH production. Signup and view all the answers

Which of the following correctly describes progesterone receptor antagonists?

They bind and block progesterone receptors. Signup and view all the answers

What is a physiological effect of progesterone?

Opposition to estrogen's effects on cervical mucus. Signup and view all the answers

Which of the following is a property of androgen activity in the ovaries?

They are produced in small quantities. Signup and view all the answers

What is the unique feature of the progesterone receptor PR-B compared to PR-A?

PR-B has additional N-terminal amino acids. Signup and view all the answers

What is a primary action of prostaglandins like PGE2 and misoprostol?

Promoting uterine contractions Signup and view all the answers

Which receptor does PGE2 bind that misoprostol does not?

EP1 Signup and view all the answers

What is a potential adverse effect of administering exogenous oxytocin during labor?

Uterine hyper-contraction Signup and view all the answers

What condition might methotrexate be used to treat?

Ectopic pregnancy Signup and view all the answers

How does methotrexate primarily affect rapidly dividing tissues?

Inhibits cell division Signup and view all the answers

What is the main purpose of a tocolytic drug?

Prevent labor Signup and view all the answers

Which mechanism do tocolytic drugs typically employ to delay labor?

Relaxing uterine smooth muscle Signup and view all the answers

What effect can elevated cellular Ca2+ have in the uterus?

Promotion of uterine contractions Signup and view all the answers

What is the primary use of mifepristone?

To terminate pregnancy Signup and view all the answers

What role do co-repressors play when estrogen receptor antagonists bind to the receptor?

They inhibit gene transcription Signup and view all the answers

Which of the following is an example of an estrogen receptor antagonist?

Clomiphene Signup and view all the answers

How do estrogen receptor agonists primarily affect gene transcription?

By recruiting co-activators Signup and view all the answers

What characterizes Selective Estrogen Response Modulators (SERMs)?

They can have varying effects in different tissues Signup and view all the answers

What is an example of an aromatase inhibitor?

Anastrozole Signup and view all the answers

What is the primary action of aromatase inhibitors in hormone therapy?

To block the production of estrogens Signup and view all the answers

Which of the following is true regarding phytoestrogens?

They are derived from plant sources. Signup and view all the answers

Which agent is commonly used as a second-line treatment following tamoxifen?

Exemestane Signup and view all the answers

What is the effect of histone acetylation in the context of estrogen receptor activation?

It relaxes chromatin structure, facilitating transcription. Signup and view all the answers

Study Notes

Estrogen Receptors

Estrogen enters the cell and binds to estrogen receptors (ER)
ER dissociates from heat shock proteins and forms homodimers or heterodimers
The ER dimer binds to estrogen response elements (EREs) on target genes
This leads to the recruitment of co-activators, facilitating gene transcription

G-Protein Coupled Estrogen Receptors

In addition to ERs, estrogen can also bind to G-protein coupled receptors (GPCRs)
For example, GPER (G protein-coupled estrogen receptor) facilitates faster, non-genomic, estrogenic activity

Progesterone Receptors

There are two progesterone receptors (PR), both derived from the same gene: PR-A and PR-B
Both have identical ligand-binding domains, but PR-A is missing the first 165 N-terminal amino acids found in PR-B
PR-B stimulates progesterone activity by recruitment of co-activators
PR-A inhibits the actions of PR-B by recruitment of co-repressors and can also inhibit transcriptional activity of other steroid receptors

Progesterone Receptor Mechanism

PR is present in the nucleus in an inactive state, bound to heat shock proteins
Progesterone receptor agonists enter the nucleus and bind to PR, leading to the dissociation of heat shock proteins
Receptor dimers form and bind to progesterone response elements (PREs) on target genes
These dimers can be homodimers (PR-A/PR-A or PR-B/PR-B) or heterodimers (PR-A/PR-B)

Physiological Effects of Estrogen

Causes endometrial proliferation
Increases the amount and water content in cervical mucus
Increases differentiation of osteoblasts and reduces the activity of osteoclasts in bone
Changes in lipid levels
Changes blood clotting factor levels

Physiological Effects of Progesterone

Causes endometrial differentiation and inhibition of proliferation caused by estrogen
Opposes the effects of estrogen on cervical mucus
Involved in the "maintenance" of pregnancy
Decline in progesterone at the end of the menstrual cycle results in the onset of menstruation

Other Ovarian Hormones

Androgens - small amounts of testosterone and other androgens are produced by the ovaries
Inhibin - an alpha-beta dimer peptide that inhibits FSH production and release
Activin - a beta-beta dimer version that promotes FSH release
Relaxin - found throughout the female reproductive system, released in response to LH, has multiple effects

Agonists, Antagonists, Both, Neither

Estrogen/Progesterone Receptor Agonists

Endogenous and exogenous estrogens can bind and activate estrogen receptors
Endogenous progesterone and exogenous progestins can bind and activate progesterone receptors

Progesterone Receptor Antagonists

Progesterone receptor antagonists (AKA antiprogestins) bind and block progesterone receptors
These drugs are used to terminate pregnancy

Estrogen Receptor Antagonists

Estrogen receptor antagonists bind to estrogen receptors and promote dimerization and binding to DNA
These drugs lead to different conformational changes that recruit co-repressors, inhibiting gene transcription

ER Agonists vs. Antagonists

ER agonists recruit co-activators - proteins with histone acetyltransferase activity that relax chromatin structure, allowing transcription machinery to initiate transcription
ER antagonists recruit co-repressors - proteins with histone deacetylase activity that tighten chromatin structure, preventing transcription machinery from binding and initiating transcription

Selective Estrogen Response Modulators (SERMs)

SERMs are ligands at estrogen receptors
They alter the conformation of ERα and/or ERβ
This conformational change is distinct from both agonists and antagonists
May lead to interaction with different co-activators and/or co-repressors in a cell-specific and promoter-specific manner

SERM Activity

These are usually partially estrogenic in some tissues and either have no activity or anti-estrogenic activity in other tissues

Indirect-Acting Agents

Aromatase inhibitors block the production of estrogens
These drugs are used for the treatment of breast cancer
Examples include: exemestane, anastrozole, and letrozole

Compounds with Estrogenic Activity

Plant-derived compounds (phytoestrogens)
Some contain progestins with less androgenic activity or that antagonizes the mineralocorticoid receptor

Combined Oral Contraceptives (COCs)

Administered for the first 21 days of a 28-day cycle
Extended cycle contraceptives (up to 84 days) are also used
Available in monophasic, biphasic, or triphasic formulations
Designed to reduce hormone exposure while maximizing anti-ovulation effects and minimizing breakthrough bleeding

COC Mechanisms of Action

Primary Mechanisms:
Estrogen inhibits FSH secretion to inhibit follicular development
Progestins inhibit LH secretion to prevent ovulation.
Secondary Mechanisms:
Progestins alter cervical mucus to impede sperm passage
Estrogens and progestins alter the endometrium to decrease implantation of fertilized eggs

COC Effects

Cervical Hypertrophy
Breast enlargement
Increased hormone-binding protein levels
Increase in plasma renin activity
Increased pigmentation of the skin
Decreased acne
Decreased hair growth
Increases in clotting and other factors
Reduced bile flow and secretion
Increased triglyceride levels
Increased basal insulin levels, reduced GI carbohydrate absorption
Increased cardiac output, blood pressure, and heart rate

Progestin-Only Contraceptives

Inhibit progesterone-dependent aspects of ovulation
Examples/dosage forms include: minipill, depot medroxyprogesterone, subdermal implants, intrauterine device
These contraceptives localize progestin levels.

Fertility

Clomiphene Citrate

Estrogen receptor antagonist used to treat anovulation
Inhibits the negative feedback of estrogen at the hypothalamus and pituitary
Results in an increase in FSH levels that enhance follicular maturation

Clomiphene Citrate Effects

Increases ovulation but inhibits estrogen's action at the endometrium
Can cause ovarian hyperstimulation syndrome and multifetal gestations
ADRs include: ovarian cysts, hot flashes, headache, blurred vision

Gonadotropins

Gonadotropins are used to induce ovulation
Daily injections of FSH are given until 1-2 mature follicles have developed
This is followed by an injection of hCG to complete follicular maturation and induce ovulation

Drugs During Pregnancy

Folic acid, antihistamines, antipsychotics, promotility agents, 5-HT3 antagonists, cannabinoids

Folic Acid

AKA vitamin B9
Several forms of folate found in diet; supplementation is with folic acid
Food sources include leafy vegetables, legumes, liver, yeast, sunflower seeds
Many foods are fortified with folic acid (e.g., pasta, bread)

Folic Acid Deficiencies

Chronic malnutrition
Chronic alcohol use
Vitamin C deficiency
Chronic liver disease
Malabsorption due to any cause

Folic Acid Metabolism

Average diet contains 500-700 mcg, 50-200 mcg absorbed
Free folic acid and monoglutamate folic acid are completely absorbed in the proximal jejunum
5-20 mg of folates generally stored in the liver, about 1-2 months worth

Folic Acid Function

Required for purine biosynthesis, thymidine biosynthesis, DNA methylation, and other metabolic reactions
Acts as a cofactor for 1-carbon transfer reactions

Nausea and Vomiting in Pregnancy

Antihistamines

Doxylamine, dimenhydrinate, diphenhydramine
Pyridoxine (vitamin B6) may also have anti-nausea effects
Promethazine is a phenothiazine antihistamine used to treat morning sickness

Antipsychotics

Mechanism of action is D2 receptor antagonism at the CTZ
Some possess antihistaminic and anticholinergic activities

Promotility Agents

Metoclopramide
Domperidone
These drugs stimulate upper GI motility without affecting the lower GI

5-HT3 Antagonists

Ondansetron
Granisetron
These agents block serotonin receptors to reduce nausea and vomiting

Cannabinoids

THC (tetrahydrocannabinol)
Several studies have indicated safety and efficacy for use in nausea and vomiting in pregnancy

Prostaglandins

Misoprostol
Actions are very similar to PGE2
Used for inducing labor, medical abortion, or as a treatment post-miscarriage

Oxytocin

Naturally produced to increase uterine contractions during labor
Exogenous oxytocin also promotes uterine contraction
Adverse effects include uterine hyper-contraction and water conservation

Methotrexate

Used to treat ectopic pregnancy, inhibiting rapidly dividing tissue
Inhibits dihydrofolate reductase, resulting in nucleic acid deficiencies

Tocolytics

Tocolytics delay or prevent labor
They typically cause uterine smooth muscle relaxation or prevent pro-contraction signaling.

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Description

This quiz explores the mechanisms of estrogen and progesterone receptors, including their structure and function. It covers estrogen receptor homodimerization, GPCR interactions, and the roles of different progesterone receptors in gene transcription. Test your knowledge on this crucial aspect of hormonal regulation.