ANS 124: Ducts - Estrogen, GH, and IGF

Estrogen is produced by what structure in the ovaries?

follicles of the ovaries

Estrogen is produced by what specific type of cells in the follicle of the ovaries?

Granulosa Cells

When Granulosa Cells secrete estrogen, where does the estrogen go right after being secreted?

into general blood circulation

What type of hormone is Estrogen?

Steroid Hormone

Estrogen is derived from what molecule?

cholesterol

Can Estrogen cross cell membranes?

Yes, it can diffuse into tissues/cells.

Is Estrogen lipophilic or hydrophilic?

lipophilic

Where does Estrogen accumulate in the body?

accumulate in fat

Estrogen binds to what receptor?

Estrogen Receptor

Where is the Estrogen Receptor located in cells?

found in cytoplasm of cells

What is the Estrogen Receptor made out of?

it is a protein

What happens to the terminal end buds of the mammary gland when a mouse is ovariectomized?

terminal end buds go away

Describe the setup of an experiment where researchers wanted to see how giving estrogen in an ovariectomized mouse would impact the end buds.

They took ovariectomized mice and put a slow release pellet in the fat pad on 1 side of the mammary gland with estrogen. They also put a placebo/control pellet on the other mammary gland.

What is a Contralateral Gland?

the opposite side to treatment

Describe the terminal end buds in the mammary gland implanted with the estrogen pellet.

Terminal End Buds started forming.

Describe the terminal end buds in the mammary gland implanted with the placebo/control pellet.

No end buds formed. The ducts are very wispy.

What are 4 examples of Steroid Hormones?

Estrogens

Progesterone

Androgens

Glucocorticoids

In the body, Estrogen can produced from what 2 places? (1 specific, 1 general)

Ovaries

Other organs like Adipose (a little Estrogen produced there)

From outside of the body, Estrogen can enter the body through what 3 ways?

Contraceptives

Diet

Environmental Contaminants

Give an example of how Diet can activate the Estrogen Receptors in the body.

Soy has isoflavones that can activate Estrogen Receptors.

Give an example of how Environmental Contaminants can activate the Estrogen Receptors in the body.

Before, Bisphenol A (BPA) was used a lot to make plastics. BPA can activate estrogen receptors.

When Estrogen binds to the Estrogen Receptor in the cytoplasm, where do they go?

go to the nucleus

When Estrogen binds to the Estrogen Receptor and goes to the nucleus, what does it act as?

a transcription factor

When the Estrogen + Receptor acts as a transcription factor, what does it do?

it binds to the DNA to regulate gene expression and produce proteins.

Ovariectomy is also called...

Oophorectomy

An Ovariectomy reduces the risk of what in women?

reduces the risk of breast cancer in women that are genetically predisposed

An Ovariectomy reduces the risk of breast cancer in women that are genetically predisposed by about ____%.

50%

What is the hazard ratio of breast cancer for the average population?

1.0

What is the hazard ratio of breast cancer for women that have undergone an ovariectomy?

0.5

What does SERMs stand for?

Selective Estrogen Receptor Modulators (SERMs)

What are Selective Estrogen Receptor Modulators (SERMs) and what do they do in the body?

Widely used class of drugs that mimic estrogen. It functions to block estrogens from binding the estrogen receptor and activating target genes.

What are the 2 most common examples of Selective Estrogen Receptor Modulators (SERMs)?

Tamoxifen

Raloxifene

What is the side effect of Tamoxifen?

it induces hot flush symptoms

Compared to Tamoxifen, Raloxifene has less side effects on what 3 areas of the body?

Raloxifene has less effects on bone, heart, and endometrium.

Tamoxifen and Raloxifene can reduce the risk of women getting breast cancer by about ___%.

50% (just like an ovariectomy!!)

Describe how the study was done to find that Tamoxifen and Raloxifene can reduce the risk of women getting breast cancer by about 50%.

A study was done with some given one of the two drugs or a placebo. The women were followed for a time period afterwards to see if they developed breast cancer.

Further experiments done revealed that estrogen does not stimulate growth in females that have had what 3 surgical procedures done?

Ovariectomized (ovaries)

Adrenalectomized (adrenals)

Hypophysectomized (pituitary)

Describe what was done in the study that revealed that estrogen does not stimulate growth when the individual has no ovaries, adrenals and pituitary.

The study did an ablation where they took out ovaries, adrenals and pituitary of a mouse to remove all hormones. Then they gave the mice a shot of estrogen and saw that the mammary gland doesn't grow.

In a mouse with no ovaries, adrenals, and pituitary, what organ needed to be present in order for the shot of estrogen to induce mammary gland growth?

Pituitary had to be present.

Specifically, what hormone of the Pituitary needed to be present in order for Estrogen to induce mammary gland growth?

Growth Hormone (GH)

What is another name for Growth Hormone?

Somatotropin

Where is Growth Hormone produced? By what type of cells?

Produced in the anterior pituitary by somatotroph cells.

Where is Prolactin produced? By what type of cells?

Produced in the anterior pituitary by lactotroph cells.

Describe the steps of what was done in a study to establish how the pituitary regulates mammary gland growth. (5 steps)

Grind up one pituitary gland (usually from bovine).

Take experimental animal that has pituitary, ovaries and adrenals removed.

Treat animal with pituitary extract.

Wait 1-7 days.

Observe responses.

In the experiment establishing how the pituitary regulates mammary gland growth, what were the 2 responses they observed after treating the animal with pituitary extract?

Mammogenic (growth promoting, increased end buds)

Lactogenic (lactation promoting)

The Mammogenic growth was due to what hormone from the pituitary?

Growth Hormone (GH)

The Lactogenic effects was due to what hormone from the pituitary?

Prolactin (PRL)

What are 3 types of experiments that you can do to determine how the pituitary affects mammary gland growth?

Remove the pituitary and determine consequences.

Administer a drug/inhibitor to block release of hormone.

Administer these hormones or an agent that induces release.

What is an example of a drug/inhibitor that blocks the release of Prolactin?

Bromocriptine

What is an example of an inhibitor that blocks the release of Growth Hormone?

Somatostatin

What is an example of a hormone that induces the release of Growth Hormone?

Growth Hormone Releasing Hormone (GHRH)

What are examples of 2 agents that induce the release of Prolactin?

A dopamine antagonist such as haloperidol/risperidone.

What do both Estrogen and GH induce in the mammary gland?

both induce end bud/duct formation

Estrogen can only work on the MG if the ______________ is intact.

Pituitary

Growth Hormone can only work on the MG if the ______________ is intact.

Ovaries

What does IGF-1 stand for?

Insulin-Like Growth Factor-1

The majority of IGF-1 is produced by what organ?

Liver

(but can be produced by other tissues too)

What type of molecule is IGF-1?

it is a protein "growth factor"

IGF-1 has high amino acid sequence similarity with what?

Insulin

IGF-1 acts on cells in the body via what receptors?

IGF-1 Receptors

During puberty, Growth Hormone increases skeleton and muscle size by doing what?

GH acts on liver and stimulates it to release IGF-1.

What are 3 potential causes of Dwarfism?

Lack of GH

Lack of GH Receptors

Lack of synthesis of IGF-1

Describe the set-up of a study that wanted to see where IGF-1 is made in the mammary gland.

Surgery was done on 65 lambs, where one side of the udder had the parenchyma removed and was left with a "Cleared Fat Pad" (no epi cells). The contralateral gland was left intact.

Describe what was sampled in the study that wanted to see where IGF-1 is made in the mammary gland. What was measured?

The mammary gland was sampled from 1 week old to pregnancy in the lambs. Collect samples from parenchyma, cleared mammary fat pad, and fat pad next to the epithelial cells.

Measure IGF-1 mRNA.

In the study that wanted to see where IGF-1 is made in the mammary gland, what was the conclusion?

IGF-1 is made in the fat pad next to the epithelial cells, NOT in the parenchyma.

The production of IGF-1 in the mammary fat pad is highest during what life stage? Why?

During puberty, because ducts are growing there.