Intro to Sex Hormones & Receptors

Question 1

Estrogens

Answer 1

eg) estradiol and estrone.

Responsible for the development and maintenance of the female reproductive system and secondary sex characteristics

Question 2

Progestogens

Answer 2

eg) progesterone
Responsible for preparation for and maintenance of pregnancy. Involved in the menstrual cycle, pregnancy and embryogenesis.

Question 3

Androgens

Answer 3

eg) testosterone
Responsible for the development and maintenance of male characteristics, includeing accessory male sex organs, and secondary sex characteristics. Androgens are also the original anabolic steroids, and the precursor for all estrogens.

Question 4

Glucocorticoids

Answer 4

Involved in the metabolism of carbohydrates proteins and fats have anti-inflammatory activity. Glucocorticoids are not normally thought of as a family of compounds essential for reproduction. They are stress hormones, and it has become a matter of interest how stress affects development.

Question 5

Where are estrogen and progesterone primarily produced?

Answer 5

Ovary (and placenta during pregancy)

Question 6

Where are androgens primarily produced?

Answer 6

Testis

Question 7

How is progesterone produced?

Answer 7

Cholesterol –> Pregnolone –> Progesterone

Question 8

How is estrone produced?

Answer 8

Progesterone –> Androstenedione –> Estrone

Question 9

How is testosterone produced?

Answer 9

Progesterone –> Androstenedione –> Testosterone

Question 10

How is estradiol produced?

Answer 10

Aromatic conversation of testosterone to estradiol by aromatase enzyme.

Question 11

What is the role of estrogen in the uterus?

Answer 11

• Estrogen stimulates the growth of the uterus by activating genes that control cell proliferation
− This can be demonstrated by measuring the uterine incorporation of [3H] thyrmidine (radiolabelled DNA base – shows the rate of DNA synthesis).
• Ovariectomy gives a small uterus
• Before puberty you have a small uterus, as not as much estrogen produced
• Embryo implants into the endometrium during pregnancy – without estrogen, this layer is much smaller, so less chance of reproductive success

Question 12

What do steroid nuclear receptors act as?

Answer 12

Zing-finger transcription factors, influencing transcription of target genes

Question 13

What 5 things to steroid receptors need to do in order to regulate?

Answer 13

1. Be in the nucleus (moving from the cytosol if necessary)
2. Bind to the hormone
3. Bind to a copy of itself to form a homodimer
4. Bind to its response element
5. Bind to other protein cofactors

Question 14

What are the 3 functional domains of steroid hormone receptors?

Answer 14

− the domain responsible for binding the particular hormone as well as the second unit of the homodimer
− the zing-finger domain needed for DNA binding to the response element
− the domain needed for the receptor to activate the promoters of the genes being controlled.

Also have a hinge region which controls the movement of the receptor (contains a NLS - this is covered by a heat shock protein. Upon binding of the hormone, the receptor releases the HSP, so the NLS is exposed, then it can translocate to the nucleus).

Question 15

What are the steroid response elements?

Answer 15

• A steroid will bind to the receptor and form the steroid-steroid receptor complex
• This complex will then bind to the steroid response element - short DNA sequences just upstream of the 5’ end
• The response element is part of the promoter of a gene. Binding by the receptor activates or represses the genes controlled by the promoter.
• The response element will only be present before certain genes, eg) estrogen activates a different subset of genes to say, progesterone because the estrogen-estrogen receptor response element is present before different genes.

Question 16

Primary and secondary responses in the transcriptional response.

Answer 16

• Steroid eg) estrogen, binds to a response element and cause an increase in the transcription of those target genes. This is the primary response
• One of those target genes may encode a protein that is itself a transcription factor, eg) progesterone.
• This transcription factor can then in turn go and activate a variety of genes to elicit a resonse. This is the secondary response.

Question 17

What are general the roles of the polypeptide hormones LH and FSH?

Answer 17

• Like the estrogens/androgens, are not male/female specific like their name suggests
• Carry signals from the pituitary to the gonads
• Without LH and FSH, there would be no steroid hormone synthesis
• When you start producing steroid hormones in puberty, it is because the gonadotrophins have been turned on.

Question 18

What is GnRH?

Answer 18

• Gonadotrophin releasing hormone is responsible for stiumulating LH and FSH release
• Has 10 amino adids
• Stimulates the transcription of the Gn alpha subunit, and the FHS and LH beta subunits.

Question 19

Where are the polypeptide hormone receptors?

Answer 19

At the cell surface, because the polypeptide hormones are water soluble and not lipophilic.