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Comparative endocrinology: summary
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Laura van den End1. Synthesis and action of
bioregulators
The endocrine system connects the brain and body. INDOLAMINES
- Synaptic: neuron releases a neurotransmitter (nt) - Derived from tryptophan → serotonin via hydro-
at synaps → picked up by receptors at the other xylation and decarboxylation (~ tyr → dopamine)
end of the synaps = local - Synthesis
- Endocrine: release signal molecules (same or 1. NAT: (+) acetyl-group to amino N ⇒ N-
similar as nt) in bloodstream (global) or body acetyl serotonin
fluids: diffuse around releasing cell (regional) 2. HIOMT: (+) CH3 ⇒ melatonin (released from
- The molecular mechanisms are similar: sometimes pineal gland (dark), circulating hormon)
involve identical molecules and receptors (a lot of - Serotonin is also released from enterochromaffin
endocrine cells are also neurons) (EC) cells to control our motility and secretion
Types of bioregulators STORAGE AND RELEASE OF AMINES
- Water soluble: amino acids, amines, peptides, and - Amines are stored in vesicles (same as released
proteins. Act through transmembrane receptors bc neurotransmitters), loaded by vesicular trans-
they can’t pass membrane (except for endocytosis) porter, released by calcium triggered exocytosis
- Lipid soluble: steroids, eicosanoids, retinoids - Similar to synaptic vesicle fusion, but hormonal
thyroid hormones. Act through nuclear receptors release into bloodstream rather dan synaptic cleft
(NR) bc they can pass the membrane = global vs local action
- Water soluble can be stored in vesicle ( - Release is controlled by control of release vesicles
lipid soluble) → control needed at the level
of synthesis = less controllable
- These are not soluble in the bloodstream
- Released on a slow time-scale → act on a
slow time-scale
Amines, peptides, proteins
Synthesis and release
PEPTIDE HORMONES
CATECHOLAMINES
- Have aromatic group, derived from tyrosine - Synthesized from genes; water soluble and act
through the same type of receptors
(derived from phenylalanine)
- Synthesis - Synthesis
1. Transcription in the nucleus
1. Trypsine hydroxylase: (+) OH ⇒ DOPA
2. Translation to preprohormone in RER
2. Dopa decarboxylase: (-) COOH ⇒ dopamine
3. Signal peptide attaches to RER membrane,
3. Dopamine β-hydroxylase: (+) OH ⇒ NA
- Make NA without 1; directly decarboxylate prohormone is packaged into vesicles
- Signal peptide → get to ER (cleaved off)
tyrosine ⇒ tyramine → hydroxylate ⇒
→ probe. Some of the probe hormone is
octodopamine
not part of the actual molecule. Only the
4. PNMT: (+) CH3 ⇒ adrenaline (more stable)
- Most of them can be nt as well as neurohormones yellow is the hormone
- Trace amines (including tyramine) are less 4. Vesicles translocate to Golgi → formation of
storage granules (dense core vesicles)
important in mammals, but more in invertebrates
- Peripheral catecholamines are metabolized by 5. Additional processing of prohormone in RER,
Golgi apparatus or storage granules
liver monoamine oxidase - Sometimes peptide hormones are short but pro-
peptide long ⇒ more copies of the same peptides
~ allows to make more of it with one precursor
Comparative endocrinology
  ↔︎
, Laura van den End
- Insulin-like peptides: disulphide bonds are formed - Ser/Thr kinase receptors: e.g. TGF-β pathway
→ middle is cleaned off by protease → end
product looks like 2 parts but come from the same
precursor (right)
- Glycoprotein hormones: Dimeric globular proteins
→ big, covered in glycosylation groups ~ allow to
be recognized by the receptor (found in all
animals, even nematodes → dimeric: α subunit
shared among animals)
Receptors and signaling GPCR (7TMS)
- Ligands can’t cross the membrane → use - Trimeric G-protein: associates with PM through
receptors: ligand specific and different ones exist lipid tail of γ subunit
for the same hormone. - Receptor stimulation dissociates α from βγ; α
- Some cells have the same receptors but don’t exchanges GTP for GDP
respond in the same way. Depending on the - Activated α interacts with downstream effectors:
downstream signaling - Gq: stimulates phospholipase C
- Gs: stimulates adenylyl cyclase
1TMS RECEPTORS - Gi: inhibits adenylyl cyclase
- Receptor kinases: GH, insulin, often long term act
- Receptor tyrosine kinases (RTK): e.g. EGF
- The Ras/MAP cascade is downstream - Turning off the response to GCPR activation
- Endocytosis of ligand-receptor complex:
fewer receptors at cell surface
- Phosphorylation of the receptor: inactivates
receptor, even if ligand-bound
- Degradation of 2nd messengers: cAMP, Ca2+
have short half-lives → need continuous prod
- Extracellular ligand degradation: removal of
ligand terminates the signal
Lipid bioregulators
- Steroids and lipid hormones ~ cross PM → bind
NR (proteins can shuttle btw cytoplasm and
nucleus) → bind DNA in nucleus → transcription
- Wether the receptor is bound to ligand affects
transfer
Comparative endocrinology
 
, Laura van den End
Synthesis
- In mitochondria and SER, from acetyl-CoA
- No storage: rate of production controls release
- Mevalonate pathway
1. Acetyl-CoA + Acetoacetyl-CoA = HMG-CoA
2. Reductase: HMG-CoA → Mevalonate
(inhibited by statins)
3. mevalonate → mevalonate-PP → isopentenyl-
PP → Geranyl-PP → Farnesyl-PP → squalene
→ → → cholesterol
- Or from diet - circulates in blood as LDL
Transport
- Non-soluble in blood
- Different steroid binding globulin use distinct
plasma binding proteins
- Corticosteroid binding globulin
- Sex hormone binding globulin
Vitamine D
- Calcitriol, secosteroid derived from cholesterol but
ring structure is broken by UV (happens in the
skin when exposed to sun) — in diet otherwise
- Converted into more active forms in the liver and
kidneys
Retinoic acid
- Isoprenoid derived from vitamine A — Important
in animal development, also as cofactor for
various lipid hormones
- Retinol is produced in plants from farnesyl
phosphate (we can’t make it) → converted into
retinoic acid in animal cells
Eicosanoids
- Lipid hormones derived from arachidonic acid (=
fatty acid, derived from acetyl-CoA)
- Involved in inflammation, modulation muscle
activity and clotting
Prostaglandins
- Small lipids derived from arachidonic acid
- Involved in pain, fever ~ aspirin affects the
conversion of arachidonic acid to prostaglandin G2
Nuclear receptors
- Lipid hormones can cross PM ~ fat soluble
- NR can bind ligand in cytoplasm → to nucleus; or
ligand crosses nuclear membrane and bind NR
- NRs are TF → control gene expression. Modular
structure: different domains ~ different functions
→ domains overlap or have multiple functions.
- Some hormones activate NR by releasing zinc
fingers from inhibitory factors → allow DNA bind
Comparative endocrinology
 
, Laura van den End
2. Hypothalamus and pituitary
- LPH ~ control lipid metabolism ~ precursor
- Neuro-endocrine cells: direct release of hormones endorphins ~ opiate-like effects on CNS and
from hypothalamic neurons ~ 3 functions PNS: inhibit release of Substance P from
1. Control of growth, metabolism and development: spinal ganglion neurons → ↓pain perception
tropic axes (HPT, HPA, HPG, HPH), prolactin - Melanotroph: α-MSH ~ control metabolism.
2. Broadcasting acute signals from the NS: Stimulates melanocytes to produce melanin
- Brain realizes it’s time to give birth →
oxytocin → birth Bold = POMC derived: POMC can be cleaved into a
- Melatonin: control of circadian rhythms variety of peptides by different PCs (prohormone
- Tells desirable behaviour of that moment convertases) → different cuts → different bits → bind
3. Homeostasis: all the cells in the body are to different receptors
surrounded by extracellular fluids → need to be
maintained ([ions] etc) Neurohypophysis
- VP → control osmotic homeostasis - Neurohemal region (posterior pituitary), not really
endocrine cells per se
The mammalian pituitary - Median eminence = pars eminens
- Most cells only secrete one tropic hormone. - Pars nervosa = neural lobe
Follicostellate cells don’t secrete hormones - Derived from diencephalon (brain)
- Axons: from hypothalamus to neurohypophysis
Adenohypophysis
- Glandular structure (anterior pituitary) The mammalian hypothalamus
- Pars distalie = anterior lobe - Part of the forebrain, one function is to mediate the
- Pars tubelaris = connection w hypothalamus nervous system control and hormone systems
- Pars intermedia = intermediate lobe - Local point of tropic (growth) hormone axes →
- Derived from neural ridge (neuro ectoderm) pws that control growth and metabolism
- Portal vessels: from hypothalamus to adenohypo
Hypothalamic areas
CELL TYPES AND HORMONES - PVN: paraventricular
- Gonadotroph (glycoprotein hormones: big dimeric - ARC: arcuate nucleus; has a morę permeable BBB
proteins that have highly glycosylated surfaces, → neurons can be regulated by hormones
same α but different β): - POA: pre-optic
- FSH ~ control release of steroids from gonads - SC: suprachiasmatic nucleus → information about
- LH: stimulate hormone production in gonads time of day
- Thyrotroph: TSH ~ controls thyroid → day to day
metabolism Hypothalamic hormones
- Somatotroph: GH: - Oxytocin (childbirth)
- Growth promoting actions can be direct or - Pars nervosa
Arginine and lysine vasopressin
via stimulation of IGF1 (adults) and -2 (fetus) - Releasing hormones
→ stimulate muscle and other somatic tissues Eminentia mediana
- Release-inhibiting hormones
- THs act synergistically with GH on several
Control the function of adenohypophysis
aspects of growth - Pituitary receptors confer specificity for releasing
- Effects of androgens/estrogens on growth are
hormones
only partly dependent on interactions w GH - Release and release-inhibiting hormones are
- Direct effects of GH on adipose tissue:
all released into the portal system
lipolysis, gluconeogenesis = release E sources - Different cell types in pars distills express
- Mammotroph: PRL ~ direct effect on target tissue.
different receptors
Most of these hormones also affect the brain (e.g - Mixture of releasing hormones controls
parental care in male fish = change in behavior)
release of tropic hormones
- Corticotroph:
- ACTH ~ control release of stress hormone:
stimulates the adrenal cortex to secrete
glucocorticoids
Comparative endocrinology
 
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