M1 Flashcards
(69 cards)
1
Q
classes of hormones
A
-
peptides: small mol of AA
- nonapeptides: 9 AA
- decapeptides: 10 AA
-
proteins: more complexity ➔ made from DNA via txl/tsl
- TSH, FSH, LH, insulin, glucagon, PRL
-
monoamines: made from AA tyrosine ➔ terminal amine + aromatic ring
- NE, EP, dopamine
-
steroids: made from CHO
- hydrophobic
- intracellular recdeptors
- estradiol, testosterone, progesterone, cortisol, aldosterone
2
Q
hormone transport
A
hydrophilic hormones
- water soluble ➔ easy to travel in blood
- cell-membrane receptors
hydrophobic hormones
- not water soluble ∴ must be bound to specific carriers/transporters to travel through blood
- globulins
- SHBG, TBG, albumin (most abundant)
- intracellular receptors
3
Q
hormone receptors
A
cell membrane receptors
-
GPCRs: 7 transmembrane passes
- G-protein is closely associated but not bound
- binding always extracellular
- binding causes conformational changes
- activates second messengers
- RTK receptor tyrosine-kinase (insulin)
- cytokine receptors (prolactin, GH)
intracellular receptors ➔ nuclear receptor superfamily
-
steroid receptor family form homodimers & are located in cytoplasm
- corticoid receptor (adrenal gland hormones)
- androgen receptor
- progesterone receptor
-
thyroid receptor family form heterodimers w/ retinoic acid receptor & are located in nucleus
- estrogen receptor (hybrid ➔ can form homo & heterodimers)
- Vit D receptor
- thyroid receptor
- retinoid acid receptor
4
Q
GPCR pathways
A
second messenger cAMP
- Gs ⍺ subunit = functional
- β & 𝛾 subunits = regulatory
- inactive when bound to β & 𝛾 subunits
- adenylyl cyclase converts ATP ➔ cAMP
-
cAMP activates PKA
- short-term effects: phosphorylates substrates outside nucleus
- long-term effects: PKA crosses nuclear envelope & finds & activates CREB to find CRE (cAMP response element = short sequences/regions of DNA w/ complementary portions for binding & txr/tsl)
- most efficient: short-term available for immediate use & synthesize more for storage for immediate release upon next signal
- ACTH, FSH
second messenger IP3 & Ca
- Gq ⍺ subunit
-
phospholipase C converts PIP2 ➔ IP3 & DAG
- IP3 released in cytoplasm & travels to ER where Ca is stored ➔ mobilizes intracellular Ca
- Ca activates calmodulin (CaM) ➔ activates CaM kinase
- DAG stays in membrane & activates PKC
- GnRH
5
Q
second messenger cAMP
A
6
Q
second messenger IP3 & Ca
A
7
Q
nuclear receptor superfamily
A
- main mechanism of action for hydrophobic hormones that bind to intracellular receptors is via transcription/translation ∴ longer response
- nuclear receptor hormones diffuse through PM
steroid receptor family form homodimers & are located in cytoplasm
- corticoid receptor
- androgen receptor
- progesterone receptor
thyroid family receptors form heterodimers w/ retinoic acid & are located in nucleus
- estrogen receptor (hybrid ➔ can form both homo & heterodimers)
- vit D receptors
- thyroid receptors
- retinoic acid receptors
8
Q
nuclear receptor action
A
steroid receptor
- steroid diffuses through PM
- receptor held together by heat shock protein (HSP) ➔ “chaperone” stabilizing protein
- HSP dissociates when steroid hormone binds to receptor
- receptor carries into nucleus & finds to & binds HRE
thyroid receptor: hormone is carried by carrier protein into nucleus b/c receptor is already bound to HRE in DNA
9
Q
neurophypophyseal neurons
A
PVN: paraventricular nucleus contains magnocellular & parvocellular neurons
- AVP
- OT
- (CRH - part of parvocellular/adenohypophysis sysyem)
&
SON: supraoptic nucleus contains only magnocellular neurons
- 80-90% produces AVP
10
Q
hypophyseotropic neurons
A
contain parvocellular neurons
Arc: arcuate nucleus
&
POA: pre-optic nucleus
PVN: paraventricular nucleus (contains both magnocellular & parvocellular)
11
Q
infundibulum
A
anatomical stalk connecting hypothalamus & pituitary gland
12
Q
hypothalamamic hypophyseal tract
A
bundle of magnocellular axons from hypothalamus to neurohypophysis
13
Q
median eminance
A
functional connection stalk btwn hypothalamus & adenohypophysis
14
Q
hypophyseal portal system
A
capillary bed where parvocellular neurons release hormones to reach adenohypophysis
15
Q
magnocellular neurons
A
- larger cell bodies
- longer axon projections that extend to the neurohypophysis
- AP opens Ca v-gated channels ➔ Ca influx facilitates fusion of hormone vesicles with PM to release hormone
16
Q
parvocellular neurons
A
- smaller cell body
- short axon projections that terminate in the hypophyseal portal system
- secrete hypophysiotropic hormones that regulate secretion of adenohypophysis hormones
17
Q
neurohypophysis
A
posterior pituitary
- where magnocellular neurons from PVN & SON end & release hormones
- glandular portion
- secretion of 2 nonapeptides: vasopressin (AVP) & oxytocin (OT)
- vasopressin = water control ➔ ↑ water reabsorption in kidneys (also regulates BP but same effect)
- oxytocin = milk release from mammary glands, contractions, & maternal behaviors
18
Q
adenohypophysis
A
anterior pituitary
- cellular portion
- somatotrophs secrete GH
- lactotrophs secrete PRL
- thyrotrophs secrete TSH
- gonadotrophs secrete FSH & LH
- corticotrophs secrete ACTH
19
Q
pineal gland
A
- tryptophan ➔ serotonin ➔ melatonin ➔ control of circadian rhythms & reproductive cycles for seasonal breeders
- synthesis of melatonin in response to light/dark stimuli
20
Q
AVP/OT precursor molecule
A
- required for proper protein folding
-
neurophysin = critical for proper protein folding
- propressophysin ➔ AVP + neurophysin II + glycopeptide
- prooxyphysin ➔ OT + neurophysin I
- precursor packed in secretory granules in Golgi apparatus & cleaved during axon transport
21
Q
AVP fx
A
vasopressin
-
regulation of water ➔ ↑ # of aquaporins & translocation to apical membrane of principal cells of the collecting duct cells of kidney
- most important fx
- V2R in kidney: GPCR that uses a Gs ⍺ subunit
-
osmoreceptors in cells detect ratio of solids to liquids
- blood osmolarity = amount of solutes in blood ➔ ↑ osmolarity (>280mOSM) = less liquid/more solutes ➔ activates osmorecdeptors
- dehydration = main signal ➔ ↑ osmolarity & cell shrinks in size ➔ osmoreceptors can sense shrinked MP
- short-term resposne: APQ2 translocation to apical membrane of principal cells to let water re-enter cells
- long-term response: ↑ expression of APQ2 & APQ3 in principal cells
-
BP maintenance ➔ vasoconstriction of vessels
- V1R = GPCR that uses a Gq ⍺ subunit
-
baroreceptors in aorta (aortic arch receptors) & carotids (carotid sinus receptors)
- stmiulation of AVP by ↓ BP/BV
- increase expression of ACTH receptors
22
Q
AVP action in kidneys
A
V2R = Gs ⍺ subunit GPCR
- AVP binds to V2R ➔ adenylyl cyclase converts ATP ➔ cAMP ➔ activates PKA
- PKA phosphorylates APQ2 ➔ activates in cytosol & allows it to transport to apical membrane for water re-entry
- water now accumulating in cell moves through APQ3 & APQ4 channels in basolateral membrane into interstitial space
- APQ2 & APQ3 = targets of AVP
- APQ4 is permanent
23
Q
diabetes insipidus
A
- consequence of AVP deficiency
- indiv cannot concentrate urine ➔ diluted urine, no smell or color
- neurogenic: caused by mutations that inactivate AVP production ➔ issue is in PVN & SON nuclei
- nephrogenic: caused by mutations in the V2R or APQ2 genes in the kidneys
-
AVP deficiency model: brattleboro rat has a genetic mutation in neurophysen II ➔ cannot fold AVP protein properly ∴ cannot synthesize AVP
- neurogenic
- symptoms: polyuria/polydipsia
- urine = 80% total fluids
- 20-30x increase in urine V than control
- ↓↓↓ osmolarity compared to control
24
Q
OT fx
A
- parturition: involved in uterine contractions during stage 2 (fetal expulsion)
- in lactation: CRITICAL for milk letdown during lactation
- critical in parental bonding & maternal behavior
25
OT action
OTR = **GPCR** associated with **Gq** ⍺ subunit: phospholipase C converts PIP2 to IP3 & DAG ➔ IP3 mobilizes intracellular Ca ➔ activates CaM ➔ activates CaM kinase & DAG activates PKC to stimulate **smooth muscle contraction**
in parturition:
* stage 1: fetal development
* **progesterone** maintains uterine quiescence during pregnancy ➔ blocks contractions (& estrogen)
* towards end of preg: ↑ estrogen & ↓ progesterone
* **estrogen** stimulates expression of OTR in myometrium & synthesis of OT
* stage 2: **fetal expulsion**
* OT stimulates contractions in uterine fundus
* mechanoreceptors sense pressure on cervix ➔ send signals through spinal cord to PVN & SON nuclei ➔ ⊕ feedback signals release of more OT ➔ **ferguson reflex**
in milk letdown:
* OT **acts on myoepithelial cells surrounding epithelial cells**
* suckling ➔ mechanoreceptors in breasts ➔ afferent signal through spinal cord ➔ stimulation of magnocellular neurons for pulsatile OT release ➔ pumping action in alveoli ➔ maximum secretion of milk
* w/out OT: cannot secrete milk ➔ no other hormone stimulates myoepithelial cell contraction in alveoli
26
all steroids come from ___________ via ___________
CHO via steroidogenesis
* steroid skeleton = 3 cyclohexane rings + 1 cyclopentane ring
* steroidogenesis involves **changes in hydroxylation & removing C**
27
CHO
* CHO biosynthesis: acetyl-CoA + acetoacetyl-CoA
* maintains fluidity of PM
* precursor mol for all steroid hormones
28
main source/site of CHO synthesis
* hepatocytes in liver ➔ de novo sunthesis
* animals must ingest ➔ cannot make enough
* CHO in PM interacts w/ GCPR & ion pumps that have specific ion binding sites for CHO ➔ pumps are deactivated if missing/depleted
29
CHO most abundant in
brain myelin sheaths
30
CHO transport in blood
via LDL (low-density lipoprotein): CHO bound to the OH group of a long chain fatty acid (has CHO + other lipids)
31
genes involved in steroidogenesis
* there are no genes for steroids but there are genes for proteins that cleave the steroids along the pathway
* 57 P450 enzymes ∴ 57 CYP genes
* 7 mitochondrial
* 50 SER
32
CYP11A1 gene encoding P450scc
location:
fx:
goal:
located in **mitochondria**
fx: 10,10-desmolase
goal: CHO side chain cleavage ➔ first step in steroidogenic pathway
33
CYP17A1 gene encoding protein P450c17
location:
fx:
goal:
locted in **SER**
fxs:
* 17⍺-hydroxylase (in zona fasciculata)
* 17,20-lyase (in zona reticulata)****
goals:
* 17⍺-hydroxylase: pregnenolone ➔ 17⍺-hydroxypregnenolone
* 17,20-lyase: 17⍺-hydroxypregnenolone ➔ DHEA****
34
CYP21A2 gene encoding protein P450c21
location:
fx:
goal:
located in **SER**
fx: 21-hydroxylation
* progesterone ➔ 11-deoxycorticosterone
* 17⍺-hydroxyprogesterone ➔ 11-deoxycortisol
* most common **mutation for congenital adrenal hyperplasia (CAH)**
35
CYP11B1 gene encoding protein P450c11β
location:
fx:
goal:
located in **mitochondria** of **ZG** cells
fx: 11β-hydroxylation
goal: 11-deoxycortisol ➔ cortisol
36
CYP11B2 gene encoding protein P450aldo
location:
fx:
goal:
located in **mitochondria** of **zg** cells
fx: 18-hydroxylation
goal: biosynthesis of aldosterone
37
3β-hydroxysteroid dehydrogenase (3β-HSD)
* located in **SER**
* **pregnenolone** ➔ **progesterone**
* 17𝛼-pregnenolone ➔ 17𝛼-progesterone
* DHEA ➔ androstenedione
38
17β-hydroxysteroid dehydrogenase (17β-HSD)
* located in **SER**
* androstenedione ➔ testosterone
* DHEA ➔ androstenediol
39
5⍺-reductase
* located in **SER**
* testosterone ➔ dihydrotestosterone
40
sulfokinase
* DHEA ➔ DHEA sulfate (DHEAS)
* weak androgen ➔ less affinity for androgen receptor
* works to maintain DHEAS storage
41
aldosterone pathway in steroidogenesis
CHO
↓ CHO desmolase (CPY11A1➞ P450scc)
pregnenolone
↓ 3β-HSD
progesterone
↓ 21-hydroxylase (CYP21A2 ➞ P450c21)
11-deoxycorticosterone
↓ 11β-hydroxylase (CYP11B1 ➞ P450c11)
corticosterone
↓ aldosterone synthase (CYP11B2 ➞ P450aldo)
aldosterone**
42
cortisol pathway in steroidogenesis
CHO
↓ CHO desmolase (CPY11A1 ➞ P450scc)
pregnenolone
↓ 17𝛼-hydroxylase (CYP17A1 ➞ P450c17)
17⍺-hydroxypregnenolone
↓ 3β-HSD
17⍺-hydroxyprogesterone
↓ 21-hydroxylase (CYP21A2 ➞ P45c21)
11-deoxycortisol
↓ 11β-hydroxylase (CYP11B1 ➞ P450c11)
cortisol**
43
androgen pathway in steroidogenesis
CHO
↓ CHO desmolase (CPY11A1 ➞ P450scc)
pregnenolone
↓ 17𝛼-hydroxylase (CYP17A1 ➞ P450c17)
17⍺-hydroxypregnenolone
↓ 17,20-lyase (CYP17A1 ➞ P450c17)
DHEA
↓ 3β-HSD
androstenedione
↓ 17β-HSD
testosterone**
44
zones of the adrenal gland
**cortex: steroid hormones ➔ derived from mesoderm of abdominal wall
* zona glomerulosa ➔ aldosterone synthesis
* mineralocorticoids ➔ aldosterone
* “minerals” ➔ regulating mineral balance (salt) in kidneys
* virtually no MC2R ➔ non-responsive to ACTH
* zona fasciculata ➔ glucocorticoids ➔ cortisol synthesis
* cortisol fx: ↑ glucose levels in blood via gluconeogenesis in liver
* majority of cortex
* most responsive to ACTH ➔ slight hypertrophy & hyperplasia
* zona reticularis ➔ androgen synthesis
* dehydroepiandosterone (DHEA)
* important for females
* responsive to ACTH
medulla: non-HPA hormones
* epinephrine
* norepinephrine
* derived from neuroectoderm: ANS/SNS**
45
CHO uptake & initiation of steroidogenic pathway
1. start with LDL
2. internalized by cell via LDL receptor
3. inside cell: LDLR + LDL is endocytosed ➔ receptor is reparated from the LDL in the endosome & LDL (CHO ester = bound to fatty acid) is hydrolyzed by CHO esterase that releases free CHO
4. LDLR recyled back to PM
5. StAR protein finds free CHO & carries to mitochondria where steroidogenesis begins
6. steroidogenesis starts in mitochondria ➔ goes to SER ➔ back to mitochondria for adrenal hormone synthesis**
46
parvocellular hypothalamaic nuclei
**PVN**
* CRH ➔ corticotroph cells secrete ACTH ➔ act on adrenal gland
* TRH ➔ thyrotroph cells secrete TSH ➔ act on thyroid gland
* AVP produced by magnocellular neurons & secreted by neurohypophysis to regulate water & BP & also produced by parvocellular neurons as a 2º stimulatory signal for ACTH release ➔ maximizes response**
**ARC**
* GnRH ➔ gonadotrophs cells secrete LH & FSH ➔ act on gonads
* GHRH ➔ somatotroph cells secrete GH ➔ act on liver
* SST: somatostatin ➔ inhibitory: ⊖ regulator of GH
* dopamine ➔ inhibitory: ⊖ regulator of PRL
**POA**
* GnRH
VIP: prolactin-releasing factor ➔ lactotroph cells secrete PRL
47
adenohypophysis hormone main fxs
positive actions ➔ stimulate glands
**ACTH:**
* synthesis of adrenal hormones
* ↑ in adrenal weight (due to ↑ activity)
**PRL**
* mammary growth
* milk synthesis
* *thermoregulation*
* *behavioral*
* *immune-related*
**TSH**
* synthesis of TH
* thyroid weight (active cells enlarge)
**FSH**
* follicle growth
* spermatogenesis
* estradiol production ➔ conversion of androgens to estrogens
**GH**
* tissue growth
* metabolic effects
**LH**
* ovulation
* testosterone production
48
ACTH action
* ACTHR = **MC2R**: melanocortin 2 receptor
* expressed in zona fasciculata & zona reticularis
* effects
* ↑ glucocorticoids (main response)
* ↑ DHEA
* ↑ adrenal weight via hypertrophy (increased secretory activity ➔ cells swell) & hyperplasia
* ↑ medullary hyperplasia ➔ ↑ release of EPI & NEPI
* ↑ expression & translocation of LDLR to membrane to facilitate LDL internalization of CHO for steroidogenesis
* intracellular activation by PKA:
* CHO esterase
* Star activated
* P450scc
* ↑ gene expression of CHO esterase, StAR protein, & P450scc**
49
ACTH response to hypoglycemia
1. stimulates PVN in hypothalamus to release CRH ➔ enters portal system
2. stimulates corticotrophs in adenohypophysis to release ACTH into systemic circulation
3. stimulates adrenal gland to produce cortisol in the zona fascicularis
4. stimulates liver gluconeogenesis
* prolonged stress response surpasses circadian rhythm
* prior high-dose synthetic glucocorticoid administration abolishes stress response
* ↑↑ adrenal hormone levels act as negative feedback to HPA axis**
50
ACTH precursor
**proopiomelanocortin** (**POMC**)
* mol have diff biological activity depending on cleavage location
* **𝛼MSH ➔ food intake, metabolic rate**
* **β-endorphin ➔ endogenous opioid**
* response depends on site of hormone synthesis & receptor
* **MC1R** in melanocytes & leukocytes of skin ➔ stimulates melanin prod
* prevents/limits further UV penetration
* repairs DNA damage
* **MC2R** for ATCH in adrenal cortex ➔ cortisol synthesis
* **MC3R** in CNS ➔ feed intake regulation
51
congenital adrenal hyperplasia (CAH)
- lack of cortisol prod during fetal development ➔ lack of ⊖ feedback for HPA axis
- results from a defficiency in an enzyme in the cortisol pathway (mutations in the CYP21A2 gene that encodes P450c21 that converts progesterone ➔ 11-deoxycorticosterone & 17⍺-hydroxyprogesterone ➔ 11-deoxycortisol)
- excess of ACTH & overstimulation of adrenal gland cause:
1. adrenal hyperplasia
2. excess prod of adrenal androgens ➔ pathway will be overactivated but the only direction it can go is towards androgens (masculinization = problematic for females)
52
systemic effects of cortisol excess
brain:
* depression
* psychosis
endocrine:
* ↓ TSH, LH, & FSH release
* ↓ GH secretion
eye: glaucoma
carbohydrate/lipid metabolism:
* ↑ hepatic glycogen deposition
* ↑ peripheral insulin resistance
* ↑ gluconeogenesis
* ↑ free fatty acid production
* overall diabetogenic effect
adipose tissue distribution: promotes visceral obesity
bone & calcium metabolism:
* ↓ bone formation
* ↓ bone mass & osteoporosis
skin/muscle/connective tissue:
* protein catabolism/collagen breakdown
* skin thinning
* muscular atrophy
immune system:
* anti-inflammatory action
* immunosuppressant
growth & development: ↓ linear growth
cardiovascular/renal:
* salt & water retention
* hypertension
GI tract: peptic ulcers
53
glucocorticoid regulation of BG
* most tissues in body express glucocorticoid receptor
* glucocorticoid effects counteract insulin: insulin inserts glucose channels to facilitate glucose uptake by tissues
* cortisol ↑ BG by inhibiting uptake in peripheral tissues & by stimulating gluconeogenesis
* "glucose sparing effect"
* catabolic effects to break apart gluconeogenesis substrates
* muscle: stimulates myostatin ➔ proteolysis to release AA
* adipose tissue: stimulates hormone-sensitive lipase (HSL) ➔ lipolysis to release FA & glycerides
* liver: stimulates PEPCK & glucose-6-phosphatase: gluconeogenic enzymes**
54
targets of cortisol in BG in homeostasis
* stimulates gluconeogenesis
* glucose-6-phosphatase
* phosphoenolpyruvate carboxykinase (PEPCK)
* stimulates glycogen synthase
* inhibits glycogen phosphorylase
* Activates lipolysis: hormone-sensitive lipase (HSL) breaks down fatty acids
* ↓ protein synthesis
* stimulates myostatin to break down muscle fibers**
55
systemic effects of chronic synthetic glucocorticoids (hyperadrenocorticism)
* ↑
* PEPCK, myostatin, lipase
* circulating AA
* BG (↑ 50%)
* ↓
* body weight ➔ change in the pattern of fat distribution: visceral fat accumulation
* muscle mass
* endogenous cortisol
* removing synthetic glucocorticoid supplementation could send indiv into hypoadrenocorticism b/c HPA axis was strongly inhibited by ⊖ feedback ➔ system doesn't resume as quickly as rx is halted
56
GCR action
held together by heat shock protein (HSP) until GC binds, then dissociates
57
clinical uses of glucocorticoids
1. allergic dermatitis
2. transplant recipients
3. inflammatory diseases ➔ potent inhibitors of immune system
58
inflammatory response
* inflammation = results of 1st line of defense (innate)
* initiated on site of antigen contact
* clinical signs:
* swelling ➔ edema from blood
* redness
* heat ➔ tons of metabolic activity generates heat
* pain
* tumor ➔ enlarged site b/c extra cells migrate to area
* loss of fx ➔ tissue busy fighting injury
59
regulation of immune system by glucocorticoids
2 levels of immune defense:
* **innate** - 1st line
* **antigen presenting cells** ➔ macrophages, dendritic cells, neutrophils
* phagocytosis of antigens at site of injury
* antigen processing & presentation
* production of pro-inflammatory cytokines: **interleukins (IL) & tumor necrosis factors (TNF)**
* **acquired** - 2nd line
* attract other immune cells
* build immune memory
* steroids act at beginning of inflammatory cascade to block entire pathway
* NSAIDs block specific parts of the pathway but not other ➔ attenuate & minimize response but don't completely stop it
60
aMSH is found in
* intermediary lobe of pituitary
* Arc
* keratinocytes (MC1R)
61
A: GnRH (females)
B: CRH + AVP
C: TSH
D: dopamine
E: GnRH
F: GHRH
G: SST (somatostatin)
62
A: corticotrophs
B: thyrotrophs
C: gonadotrophs
D: somatotrophs
E: lactotrophs
63
A: ACTH
B: TSH
C: PRL
D/E: LH & FSH
F: GH
64
parvocellular neurons
A: POA
B: PVN
C: Arc
65
what hormone stimulates OT receptors & OT
estrogen
66
precursor for oxytocin
prooxyphysin
67
precursor for vasopressin
propressophysen (neurophysen II + glycopeptide)
68
**glomerulosa**
hormone B: pregnenolone
enzyme E: 3β-HSD
hormone C: progesterone
enzyme G: P450c21
enzyme H: P450c11
enzyme J: P450aldo
**fasciculata**
* enzyme B: P450c17
* hormone D: 17⍺-hydroxypregnenolone
* enzyme E: 3β-HSD
* enzyme H: P450c11
* hormone O: cortisol
**reticularis**
* enzyme C: 17,20-lyase
* hormone F: DHEA
* enzyme F: sulfokinase
* hormone J: DHEAS
* enzyme E: 3β-HSD
* hormone H: androstinedione
* enzyme D: 17β-HSD
69
* hormone B: pregnenolone
* enzyme E: 3β-HSD
* hormone C: progesterone
* enzyme G: P450c21
* hormone K: 11-deoxycorticosterone
* enzyme H: P450c11
* hormone M: corticosterone
* enzyme J: P450aldo
* hormone N: aldosterone
* enzyme B: P450c17 ➞ 17⍺-hydroxylase
* hormone D: 17⍺-hydroxyprenenolone
* hormone E: 17⍺-hydroxyprogesterone
* hormone L: 11-deoxycortisol
* hormone O: cortisol
* enzyme C: P450c17 ➞ 17,20-lyase
* hormone F: DHEA
* hormone H: androstinedione
* enzyme D: 17β-HSD
* hormone I: testosterone
* hormone G: androstinediol
