What is the most important gland?
a signaling molecule that regulates physiology and behaviour
Name 5 types of hormones
peptide, steroid, eicosanoid, amine, and glycoprotein
derived from amino acids, insulin
derived from cholesterol, testosterone
derived from lipids, prostaglandin
derived from the amino acid tyrosine; two categories: catecholamine (epinephrine) and thyroid hormones (T3)
category of amine hormones, epinephrine
category of amine hormones, T3
derived from amino acids with carbohydrate side chains, FSH
Hormones vs. NTs
H: large spatial and temporal scales, slow transmissions w/ continuously variable action, specific receptors NT: small scale, quick transmission, all-or-nothing action
Name the axis that controls the development and regulation of reproductive and immune systems
the hypothalamus-pituitary-gonadal axis
Walk through the HPG axis
the brain releases gonadotropin-releasing hormone (GnRH) to anterior pituitary which releases LH and FSH. these cause ovaries to make estrogen and progesterone. they cause testes to produce testosterone
Name the axis that VTG works on
the hypothalamus-pituitary-gonadal-liver axis
Bis(2-ethylhexyl) phthalate (DEHP)
What is the ligand-activated transcription factor of estradiol?
the estrogen receptor
What is the ligand-activated transcription factor of cortisol
the glucocorticoid receptor
What is the ligand-activated transcription factor of all-trans-retinoic acid?
Retinoic acid receptor
What is the ligand-activated transcription factor of fatty acids?
peroxisome proliferator-activated receptor
What is the ligand-activated transcription factor of androstenol
contitutive androstane receptor
What is the ligand-activated transcription factor of pregnolone and progesterone
pregnane X receptor
What is the endogenous ligand of ER
What is the endogenous ligand of glucocorticoid receptor
What is the endogenous ligand of retinoic acid receptor?
What is the endogenous ligand of aryl hydrocarbon receptor
it is unknown
What is the endogenous ligand of PPARa
What is the endogenous ligand of constitutive androstane receptor
What is the endogenous ligand of pregane X receptor
pregnenolone and progesterone
Walk through the HPGL axis in oviparous organisms
GnRH tells anterior pituitary to release GTHI and GTHII which tell the gonads to tell E2 to tell the liver to make VTG and ZRP and go to the gonads, which then send E2 to teh hypothalamus
What is the name of the nervous system in invertebrates?
what are the four main targtes of EDCs?
- hormone synthesis
- hormone transport
- hormone degradation
- hormone action
hormone syntheis as a target
big target is steroidogensis. the rate limiting step in steroidogensis is the conversion of cholestrol to pregnenolone by Steroidogenesis Acute Regulatory Protein. all other steroids are derived from pregnenolone
Name three "transport proteins" that are for hormones
corticosteroid-binding globulin (CBG)
sex-steroid binding globulin (SSBG)
EDCs tend to interact with hormones that bind with what kind of receptors?
Where on nuclear receptors do hormones bind?
the ligand binding domain
what does E2 aid in in vertebrates
reproduction, the cardiovascular system, bones, indirectly aid thyroid hormone action
What is the purpose of Tier I assays?
Name three tier I systems
they evalute whether the substance has the potential to interact with the hormone system
- ER competitive binding assay
- yeast reporter gene assay
- E-SCREEN assay
What are the limitation of Tier I assays?
they focus on receptor-mediated effects, but some EDC cause non-receptor-mediated effects. they could alter enzyme activity, change transduction pathways...
What is so special about the H295R Steroidogenesis Assay?
it can detect non-receptor mediated effects and you don't have to kill whole animals to run it
What is the purpose of Tier II assays?
What are three types?
they confirm endocrine distrupting effects and dose-response info to be used for risk assessment
- mouse uterotropic assay
- full life cycle tests
- two-generation reproductive toxicity tests
What is the jost paradigm of sexual differentiation
Sexual differentiation can be viewed as a sequential process beginning at the moment of conception when chromosomal sex is established. the gonads then differentiate into ovaries or testes, and the consequence of this gonadal differentiation is binary sexual phentype development
In things like birds, mammals, and amphibians, what are the dependent factor of sexual determination
in reptiles, what factor controls sexual determination?
Define sexual differentiation
the embryonic process of developing into a male or female
The Y chromosome causes the expression of what gene that initiates male development?
The SRY gene
Before sexual determination, the gential ridge must on a bipotenial gland called the _____? What does it develop into in males and in females?
Mesonephros: testes and ovaries
what the word for undescended testicles?
whats the word for when the urethra develops on the underside of the penis?
What was the main adverse effect of DES
organogenesis exposure disrupting differentiation of estrogen responsive organs, led to vaginal and cervical clear cell adenocarcinoma
Where does DES bind?
the alpha estrogen receptor in utero
talk about gene imprinting
DES does this, it's an epigenetic response, DNA methylation alters transcription, histone modification alters chromatin structure, thus altering gene expression
does DES or E2 have stronger binding affinity for sex-steroid hormone binding globulin? what are the implications of this?
E2 does. so that means DES will be unbound extracellularly, thus more bioavailable and capable of passing intracellularly
What is EE2
17 alpha-ethinylestradiol is a potent synthetic estrogen used in oral contraceptives
what is BPA
bisphenol-a is a monomer of plastics (#7, baby bottles, dental devices), structurally similar to DES, weak ER agonist, much weaker than E2
what are the four main low dose chronic processes of concern causing BPA exposure?
- hot coffee epoxy resins
- microwaving plastics
- chewing toys for dogs, babies
- canned goods lined with epoxy resin/things stored in plastic
phthalates are agonists of what receptor?
peroxisome proliferator-activated receptor-alpha, a nuclear receptor abundant in the liver, regulates cell differentiation, functionally inactive in primates
what is the most commonly used alkylphenol, and what is the name of its dangerous degradation product
nonylphenol polyethoxylate, and nonylphenol
NPs are in waterway at pg/L levels, why do we care?
because they are lipophilic and have high bioconcentration factors. affect aquatic species' seual development, differentitation and reproduction