2. ● primarily in birth control
● hormone-replacement therapy (HRT)
● inflammatory conditions
● cancer treatment
Steroid hormones used
3. General groups of steroid hormones
1. Estrogens
2. Progestins
3. Androgens
4. Glucocorticoids (GCs)
5. Mineralocorticoids (MCs)
4. Steroid Hormone Receptors
Steroid hormones regulate tissue-specific gene expression.
Estrogens such as estradiol increase uterine cell proliferation,
for example, but not prostate cell proliferation.
Androgens such as testosterone do the reverse.
Neither androgens nor estrogens affect stomach epithelium.
5. key players in gene expression (novel membrane receptors)
other proteins for example,
Chaperone proteins help fold the receptor proteins into the
proper three-dimensional shape for binding the steroid ligand.
steroid hormone receptor and associated proteins make up the
mature-receptor complex.
Transcription occurs when all the necessary associated proteins
have been recruited to the DNA–receptor complex.
Steroid Hormone Receptors
6. some effects of steroid hormones are mediated via rapid,
nongenomic mechanisms. (classical steroid hormone
receptors) whereas others rely on (novel membrane receptors)
Steroid Hormone Receptors
8. The complementary DNAs (cDNAs) of all the major steroid hormone
receptors have been cloned, giving the complete amino acid sequence
of each.
The organization of the domains for all types of steroid hormone
receptors is the same, but the number of amino acids for each receptor
varies.
Structure of Steroid Hormone Receptors
10. Structure of Steroid Hormone Receptors
N-terminal (A/B) domain : Once the steroid–receptor complex has
bound to the target gene(s) (called the A/B modulator domain)
1. activates the hormone response elements adjacent to the
genes.
2. activates the hormone response elements are on the DNA
adjacent to the target gene.
They contain about 12 to 18 base-pair DNA sequences and consist
of two “half sites” that are separated by a variable spacer.
11. In the nucleus, steroid hormone–receptor complexes exist as dimers;
the dimeric structure allows access to both half sites.
The nucleotide sequence and spacing between the half sites are
essential for the specificity of the various steroid–hormone complexes.
Structure of Steroid Hormone Receptors
12. Structure of Steroid Hormone Receptors
DNA-binding (C) domain.
about 65 amino acids
two zinc finger motifs that are important for recognition and binding
to the DNA response elements.
The zinc fingers are also responsible for dimerization of the receptor.
13. Structure of Steroid Hormone Receptors
Hinge (D) domain.
variable linker region involved with nuclear localization and transport
(translocation) of the steroid–receptor complex into the nucleus.
14. C-terminal ligand-binding (E) domain (LBD).
about 250 amino acids.
This section has the steroid hormone–binding site and is also
involved with ligand-dependent transcriptional activation,
receptor dimerization, and in some cases, repressing
(“silencing”) particular genes.
Structure of Steroid Hormone Receptors
16. Estrogen receptors alpha (ERα) and beta (ERβ), which are encoded
by different genes.
ERα :uterus, vagina, and ovaries, breast, the hypothalamus,
endothelial cells, and vascular smooth muscle.
ERβ : ovaries and the prostate, with reduced occurrence in the
lungs, brain, and vasculature.
ESTROGEN RECEPTORS
ligands
17. PRA , PRB but these are derived from a single gene.
PRA has had 164 amino acids truncated from the N-terminus of PRB
PRB mainly mediates the stimulatory actions of progesterone.
PRA acts as a transcriptional inhibitor of ER, AR, GR, MR, and PRB.
result of interactions with different coactivators and corepressors.
The DNA- and ligand-binding domains for the two receptors are identical.
PROGESTERONE RECEPTORS
18. ดัดแปลงจาก Pateetin P, Hutvagner G, Bajan S, Matthew PP, Eileen MM, Boonyaratanakornkit V. Triple SILAC identified
progestin-independent and dependent PRA and PRB interacting partners in breast cancer.
164
amino
acids
19. The AR, GR, and MR are present in only a single form.
Only one gene and one protein are known for each receptor.
Mutant forms of AR and GR are known, and evidence is mounting that
some of these mutant receptors are associated with disease states.
ANDROGEN, GLUCOCORTICOID, AND
MINERALOCORTICOID RECEPTORS
22. biosynthesized from cholesterol (from acetyl-
CoA via the mevalonate pathway)
a greater amount (about 1 g) is biosynthesized
per day.
Steroid Biosynthesis
HSD =
hydroxysteroid
dehydrogenase
23. Conversion of cholesterol to pregnenolone is the rate
limiting step in steroid hormone biosynthesis.
It is not the enzymatic transformation itself that is
rate limiting
however, the translocation of cholesterol to the inner
mitochondrial membrane is rate limiting.
Steroid Biosynthesis
31. • ถ้าสารตังต้นเป็น 17α –hydroxyprogesterone ตัว
lyase จะทําให้เกิด androstenedione ซึงพบเฉพาะใน
มนุษย์
• DHEA is converted to androstenedione by the
action of 3β-HSD
Steroid Biosynthesis
