9-1 Steroid and Lipophilic Signaling Gaddy R

Terms	Definitions
Name this steroid hormone. The answer is on the following card.
Testosterone	Testosterone
Name this steroid hormone. The answer is on the following card.
estradiol	estradiol
Name this steroid hormone. The answer is on the following card.
Progesterone	Progesterone
Name this steroid hormone. The answer is on the following card.
Cortisol	Cortisol
Name this steroid hormone. The answer is on the following card.
Aldosterone	Aldosterone
Name this steroid hormone. The answer is on the following card.
Thyroid Hormones	Thyroid Hormones
Name this steroid hormone. The answer is on the following card.
Vitamin D3	Vitamin D3
Name this steroid hormone. The answer is on the following card.
Retinoic Acid	Retinoic Acid
What are the three sex steroids from above?	testosterone, estrogen, progesterone
What are the two corticosteroids from above?	cortisol and aldosterone
What is the function of the glucocorticoids?	Glucocorticoids are corticosteroids that stimulate production of glucose
What is the function of mineralocortidoids?	Minalocorticoids are corticosteroids that act on the kidney to regulate salt and water balance
Thyroid hormone is synthesized from ______ in the thyroid gland; it is important in development and metabolism.	tyrosine
What are the main functions of Vitamin D3	regulates Calcium metabolism and bone growth
Retinoic acid and related retinoids are synthesized from ______ and play important roles in development.	Retinoic acid is synthesized from Vitamin A
Receptors for cortisol, estrogen, progesterone, vitamin D, thyroid hormones, and retinoic acid are members of the _________.	nuclear receptor superfamily
In each of the superfamily receptors, the ligand-binding domain is nearly the same size; however, specificity for a receptor comes from the _______.	DNA-binding domain
_______ serves as an inhibitory protein to mask the DNA-binding site.	HSP (heat shock protein); a hormone binds the hormone binding site in order to release the HSP
_________ increase the half-life of steroids in the circulation and extracellular space prior to entry into the cell.	steroid hormone binding globulins (SHBG)
After release from the SHBG, the steroid can enter the cell and bind to its receptor. The receptor complex can then bind to the _______ on the DNA strand.	steroid response element (SRE)
The mechanism described above is one of _______ steroid hormone action.	this is the Classical Mechanism of Steroid Hormone Action
The classical mechanism of steroid hormone action is ligan-dependant DNA binding. In the example of glucocorticoid, the receptor is bound to _______ in the absence of the hormone. Binding displaces this factor and leads to binding of regulatory DNA sequences and transcription.	receptor is initially bound to Hsp90.
True/False Hormone receptors are only in the cytosol.	False; the receptor could be either in the cytosol or nucleus.
The receptor will bind as a ______ to the DNA strand.	dimer
The coactivator that binds with the receptor dimer is ______.	HAT (histone acetyltransferase)
In the non-classical mechanism of nuclear receptor gene transcription, the _______ binds DNA in the absence of a ligand.	inactive receptor
_________ hormone works by a ligand independent mechanism.	thyroid hormone
In the absence of hormone, the hormone receptor is associated with a corepressor complex, such as _______, and represses transcription of target genes.	histone deacetylase (HDAC); thyroid is the main example here. it must go straight to the receptor that is already bound to the DNA. HAT is still a coactivator here.
Describe how estrogen modulates transcription activation through non-traditional signaling.	There are two kinds of estrogen receptors, alpha and beta. Two alphas can be be bound by estrogen receptors and bind as a homodimer to the Estrogen Response Element (ERE). However, an alpha/beta heterodimer or beta/beta homodimer can bind other EREs not for estrogen. This is non-traditional signaling and it is a way in which estrogen gene regulation is modulated.
In non-traditional steroid receptor regulation of transcription, specificity is determined by the co-factor involved. Two examples of co-factors given that work in this manner were _____ and _____.	Sp1 and Ap-1 (involves binding of a heteromer); this is modulation rather than activation, such as with ERE above.
The non-traditional modulation described above may not be only activation, but also repression. In the case of NFkappaB. It usually activates transcription when the IkappaB dissociates. However, even when IkappaB is dissociated and NFkappaB is activated, _________ binding to the estrogen receptor can still repress transcription.	Estradiol binding
Of the variations in steroid hormone-regulated gene transcription, the ________ mechanism involves ligand-dependent receptor binding to SREs on DNA and transcription	Classical
The ________ mechanism involves ligand-independent receptor binding to SRE on DNA, ligand binding activates transcription (eg. thyroid hormone receptor)	non-classical
The ________ mechanism involves ligand-bound receptors that bind to other transcription factors to modulate transcription on their cognate DNA elements or non-SRE containing sequences.	non-traditional
Just as normal hormone binding facilitates receptor dimerization and exposure of activation domains and DNA binding domains, __________ binding of an antagonist prevents activation and coactivator binding. _______ domains are instead exposed and bound to prevent transcription.	Anti-hormone binding prevents activation and exposes repressor domains for the binding of co-repressors to prevent transcription
________ is a drug that binds estrogen receptor alpha and suppresses ER activities such as breast epithelial cell proliferation.	Tamoxifen
_______ is a drug that binds to progesterone receptors and prevents progesterone-dependent gene transcription needed for uterine epithelial and stromal changes normally required for embryo implantation.	Mifepristone (RU486)
________ are factors that bind to estrogen receptors with unique affinity and create unique conformational changes in the receptor to target specific co-factor binding and alteration of gene transcription.	Selective Estrogen Receptor Modulator (SERM); SERM interact differently with estrogen receptors to enable different modulation of transcription
________ is used as a treatment for osteopenia based on its characteristics as a SERM. I has agonistic effects on bone via RREs, but antagonistic effects on breast tissue via suppression of ERE-dependent transcription.	Raloxifene
________ interact selectively with steroids and ultimately are involved in activation of transcription. They have ligand selectivity and potential for cross-communication between pathways.	Steroid Receptor Coactivators (SRCs)
Nitric oxide is formed by through the enzyme_______ and the investment of NADPH to form NO and citrulline from arginine.	nitric oxide synthase
Nitric oxide is a _______ signaling molecule in the nervous, immune, and circulatory systems, which alters the activity of enzymes.	paracrine signaling molecule
NO binds to the _____ group of Guanylyl Cyclase.	heme
This binding allows for GTP substrate to form and make it possible to form ______.	cGMP
Guanylyl cyclase is activated in ______.	smooth muscle cells; though NO comes from endothelial cells, i.e. paracrine
Ach releases _______ to activate NO synthase to co-opt a pathway and make NO.	Ca2+/Calmodulin
______ is a medication that can quickly convert to NO in the blood and increase blood flow to the heart.	Nitroglycerin
Drugs for erectile disfunction often target _______ in the NO/cGMP pathway. Inhibition of the activity of this enzyme prevents breakdown of cGMP to GMP. cGMP is a precursor in the pathway to smooth muscle relaxation and arterial dilation.	PDE5
Familiarize yourself with this pathway.
In a separate guanylyl cyclase path, a single transmembrane ligand is activated by __________, to convert GTP to GMP.	atrial naturetic peptide (ANP)
Describe the mechanism for sight and how ED treatment drugs might affect it.	In the mechanism for sight, light activates Rhodopsin, which separates Alpha and beta subunits of Transducin yielding an Alpha GTP. The Alpha-GTP binds to phosphodiesterase to turn cGMP to GMP. This closes the cGMP gated Sodium channel, depolarizing the rod cell membrane. Since cGMP comes from GTP via Guanylyl cyclase, this drug affects two pathways. Viagra can lead to phosphodiesterase inhibition in this pathway.
_____ is similar to NO in that it can cross the plasma membrane and stimulate Guanylyl cyclase.	CO
________ are lipid signaling molecules which include prostaglandins, prostacyclin, thromboxanes, and leukotrienes. They can act in autocrine and paracrine pathways.	Eicosanoids
Eicosanoids are synthesized from arachidonic acid, which is formed from phospholipids. Arachidonic acid is converted to prostaglandin H2, catalyzed by cyclooxygenase. There are two forms of cyclooxygenase: _______ and _______.	COX-1, which results in normal production of prostaglandins COX-2, which results in increased prostalandin production associated with inflammation and disease.
_________ is a rate limiting factor for formation of all of the eicosonoid family. Inhibiting A2 would slow eicosonoid formation.	Phospholipase A2 (PLA2)
Glutamate triggers prostaglandin signaling. This is a ________ signal in regard to the glutamate. It is an _________ signal in regard to prostaglandins.	paracrine for glutamate; autocrine for prostaglandins