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Endocrinology > Lesson 25 Medical uses of endrogen > Flashcards

Lesson 25 Medical uses of endrogen Flashcards

1
Q

Seven therapeutic uses of female reproductive hormones

A
  1. Fertility treatments
  2. In vitro fertilization
  3. Contraception drugs
  4. Hormone replacement therapy
  5. Antagonists for cancer therapy
  6. Drugs for prevention of menopause symptoms
  7. Treatment of brain injury
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2
Q

What does hypothalamus release to influence gonads?

A

GnRH to anterior pituitary

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3
Q

What does anterior pituitary send to gonads?

A

FSH, LH

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4
Q

What is FSH and its role?

A

follicle stimulating hormone; primordial, secondary and mature follicles develop under FSH

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5
Q

What develops under FSH and estrogen?

A

Secondary and mature follicles, leads to ovulation

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6
Q

What develops under LH

A

Mature follicle undergoes ovulation, then becomes mature corpus luteum

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7
Q

Under the influence of progesterone and estrogen, what happens to corpus luteum?

A

Mature and the involuting corpus luteum

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8
Q

How does ovarian cycle coincide with endometrial cycle?

A

Estrogen released by secondary and mature follicles induces proliferative cycle of endometrium. Secretion of progesterone and estrogen from mature corpus luteum induces secretory and ischemic phase.

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9
Q

Stages of menstrual cycle

A

Days
1-5 E and P are low because CP is regressing, so a. endometrial lining sloughs, b secretion of F and L is released from inhibition, stimulating follicle growth
7 single follicle dominance
7-12 plasma E up because of secretion by dominant follicle. Endo proliferates
7-12 L and F decrease due to E an inhibit negative feedback. nondom. Follicles degenerate
12-13 L surge induced by up plasma E so a. oocyte first erotic division and b. follicle stimulated to secrete digestive enzymes and prostaglandins
14 ovulation
15-25 CL forms, secretes E and P. secretory Endo develops. Secretion of F and L inhibited (no new follicles)
25-28 CL degenerates if egg not fertilize3d

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10
Q

3 drugs used in IVF stimulation protocols in US

A

GnRH-agonist (Lupton), or GnRH-antagonist (ganirelix) suppresses LH surge and ovulation until follicles are mature
FSH stimulates devt of multiple follicles
HCG cause final maturation of eggs

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11
Q

How is GnRH secreted?

A

In a pulsatile manner with one pulse occurring approx.. each hour

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12
Q

What happens when there is administration of long-acting GnRH analog?

A

Induces initial stimulation of LH and FSH but over a few days causes complete desensitization of pituitary gonadotroph

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13
Q

What does loss of endogenous GnRH induce?

A

Loss of GnRH receptors and the LH response to a bolus injection of GnRH is very low

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14
Q

The in vitro fertilization process

A
  1. Woman is given hormone treatments to stimulate egg production
  2. Multiple eggs are taken from the woman’s ovaries
  3. In the lab, the eggs are mixed with the man’s sperm cells in a culture dish to become fertilized
  4. The fertilized eggs, or embryos, are placed in an incubator for about 48 hours
  5. Embryos are implanted in the woman’s uterus or frozen for future implanting
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15
Q

How to test genetics of in vitro fertilization?

A

Use biopsy needle to remove polar body

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16
Q

Methods of hormonal contraception

A

Oral contraception, injectable/implant progestin, morning after pill, IUD, antiprogestin RU 486, suction, D&C

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17
Q

How do contraceptive steroids work?

A

inhibit LH surge and ovulation

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18
Q

Examples of contraception steroids

A

Ethinyl estradiol(estrogen) and norethindrone(progesterone)

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19
Q

How does progestin affect steroidogenesis and ovulation?

A

As nongestin rises, LH and Estradiol flatten out and are not available. Small peak in middle of cycle.

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20
Q

What will low levels of progesterone cause between 4-8 weeks of pregnancy?

A

Miscarriage. Introduction of progesterone antagonist bet. 4-8 weeks also induces miscarriage

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21
Q

How was DES used in 50s and 60s? What changed?

A

To prevent miscarriage. But DES was shown to have preventive effect on miscarriage, but created numerous health problems (early onset of uterine cancer and malformation of genital tract of daughters whose mothers were treated with DES during pregnancy)

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22
Q

How did meat producers use DES?

A

To increase meat production

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23
Q

What is tamoxifen

A

An estrogen antagonist used to treat breast cancer patients with estrogen-responsive cancer.

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24
Q

What has long term use of HT in older menopausal women been associated with?

A

Increased risks for venous thromboembolis, coronary events, stroke and breast cancer

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25
Estrogen regulation of bone turnover
Estrogen affects osteocytes, osteoblasts, T-cells and osteoclasts
26
Estrogen and osteocytes
decrease in apoptosis/ other mechanisms results in decrease in activation of bone remodeling
27
Estrogen affects osteoblasts
decrease in apoptosis, oxidative stress, NF-kB activity, other mechanisms, leads to maintenance of bone formation
28
Estrogen affects osteoclasts
Rise in apoptosis, decrease in RANKL-induced differentiation, leads to decrease in bone resorption
29
Main effect of estrogen on bone remodeling?
Inhibited bone remodeling, probably via osteocyte
30
How does estrogen affect bone resporption
Inhibits it. Directs effects on osteoblasts, although effects of estrogen on osteoblasts/osteocytes and T-cell regulation of osteoblasts probably also play a role
31
What is estrogen deficiency associated with in bones? Why?
A gap between bone resorption and bone formation. Due to loss of effects of estrogen on decreasing osteoblasts apoptosis, oxidative stress, osteoblasts NF-kB activity, and perhaps other as yet undefined mechanisms.
32
What does estrogen block via osteocytes, osteoblasts and T-cells?
The activation of osteoclasts
33
How do bisphosphonates affect osteoclasts?
1. They inhibit osteoblasts formation, migration and osteolytic activity. They promote apoptosis. 2. Modulate signaling from osteoblasts to osteoblasts 3. Local release during bone restoration 4. Concentrated in newly mineralizing bone and under osteoclasts
34
What kind of cancers are estrogens a major player of?
Hormone-dependent cancers
35
In what kind of tumors has E2 been implicated?
Breast, ovarian, endometrial, prostate, colon and thyroid tumors
36
What is estrogen action mainly mediated by?
the ERs
37
What are ERs a target for?
They are molecular targets for the discovery of novel drugs towards the improvement of endocrine treatment in hormone-sensitive cancer
38
What kind of compounds modulate ER activity?
Pure anti-estrogens, which completely inhibit ER signaling SERMs, which display partial ER agonist/antagonism mechanism-specific legends acting downstream ER activation Inhibitors of aromatase enzymatic activity, which increases estrogen availability at tissue levels converting androgens into estrogens
39
What are Selective Estrogen Modulators (SERMs)s?
A class of compounds that act on the estrogen receptor.
40
How are SERMs different from pure receptor agonists and antagonists?
Their action is different in various tissues, thereby granting the possibility to selectively inhibit or stimulate estrogen-like action in various tissues.
41
What are phytoserms?
Scientifically accepted SERMs from a botanical source
42
What happens to the ER upon binding an agonist or antagonist?
It undergoes a conformational change that permits its spontaneous dimerization and facilitates the subsequent interaction of the diner with estrogen response elements (ERE) located within target genes.
43
Which two ERs have been identified?
ER (alpha) and ER beta, which have the potential to form homodimers or heterodimers in cells where both subtypes are expressed.
44
How do different ligands have different effects on ER structure?
Receptor coactivators (CoA) interact with agonist-activated ER and facilitate transcriptional activation. Corepressors interact with antagonist-activated receptor and help to maintain it in a quiescent state.
45
What do SERMs permit ER receptors to do?
To adopt a structure that is intermediate between that observed following the binding of agonists or antagonist.
46
What does tamoxifen do?
It decreases the cumulative number of cases of invasive breast cancer.
47
Raloxifene
Synthetic estrogen that may decrease risk of osteoporosis and breast cancer?
48
What are good and bad effects of raloxifene?
``` Good effects: 1. Strengthens bones 2. Lowers LDL cholesterol 3. May reduce breast cancer risk 4. May reduce uterine cancer risk Bad effects 1. Increases blood clot risk 2. No relief from hot flashes ```
49
What kind of receptors does estrogen use?
Nuclear receptors and plasma membrane receptors
50
How are estrogen receptors different?
Estrogen elicits rapid cellular response via plasma membrane receptors separate from the nuclear receptors.
51
Do other steroid hormones have membrane-bound receptors? What is their purpose?
Yes. Generally involved in rapid cellular response.
52
Endocrine disruptors
Chemical substances present in the environment which may deleteriously affect hormonal balances in the body and interfere with reproduction.
53
Which compounds have anti-androgenic properties?
Fungicides, pesticides, herbicides, flame retardants, surfactants
54
What are the most studied ED chemicals?
Plasticizers biphenyl and phthalates
55
How were BPA epoxy resins used?
Protective coatings on metal equipment, piping, steel drums, and the interior of food cans, as well as adhesives used to lay flooring and seal teeth.;
56
What was second use found for BPA?
When polymerized, it forms a hard plastic called polycarbonate. Used in electronics, safety equipment, automobiles and food containers.
57
Association between very-low-dose exposure to BPA and?
Adverse health effects, including breast and prostate cancer, obesity, neurobehavioral problems, and reproductive abnormalities.
58
How is phthalate used?
Provide flexibility to polyvinylchloride. Ubiquitous in toys, packaging, medical tubing and blood storage bags, insecticides, lubricants. Also, skin care products, cosmetics and medication.
59
What does phthalate interfere with?
Production of testosterone and development of male reproductive tract.
60
What have epidemiological studies linked exposure to phthalate to?
Various health issues such as increase incidence of obesity, diabetes, learning disabilities, and behavioral problems in children;

Endocrinology (21 decks)

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