Transcript AnS 536 Module 11 Endocrine Day 1 presentation Ben D 2016x

Endocrinology
Overview
O Hormone classification
O Endocrine organs
O Hormones
Hormone classifications
O Steroid
O Estrogen
O Testosterone
O Protein
O PRL
O ACTH
O Glycoprotein
O FSH
O LH
O Fatty acid
O PGF2a
O Peptide
O GnRH
O Oxytocin
O Neurotransmitter
O PIF
O PRF
O Amino acid derivative
O Melatonin
Endocrine Organs
O Pancreas
O Pineal
O Hypothalamus
O Parathyroid
O Pituitary
O Paraventricular
O Anterior
O Posterior
O Adrenal gland
O Thyroid
Nucleus
O Thymus
O Ovaries
O Testis
Steriodogenic Pathway
Important hormones
O
O
O
O
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O
O
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O
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O
GnRH
FSH
LH
Progesterone
Estrogen
Prostaglandid F2a
Adrenocorticotropic hormone
Cortisol
Oxytocin
Relaxin
Insulin
Glucagon
IGF-1/IGF-2
Gastrin
Bombesin
Important hormones
O
O
O
O
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O
O
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O
Parathyroid hormone
Thyroid stimulating hormone
Thyroid hormone
O
Thyroxine (T3)
O
Triiodothyronine (T4)
O
Reverse T3
Growth hormone
Testosterone
DHEA
Prostaglandin E
Growth hormone inhibiting/releasing hormone
Epidermal growth factor
Vasoactive intestinal peptide
Aldosterone
Placental growth hormone
Placental lactogen
Prolactin
Melanocyte stimulating hormone
Melatonin
Gastrin
O Secreted from G cells
O G cells throughout the
intestinal tract, highest
concentration in the
antral portion of the
stomach/abomasum
O Gut specific actions,
mildly trophic effect on
the pancreas
Gastrin
O High gastrin concentration during
perinatal period in rats, other
mammals
O Development of gastric activity in part
due to gastrin
O In suckling rats:
O Antral levels low, rise on day 20
O Day 22—gastrin reaches adult levels
O After day 25—antral/serum levels decline
to basal levels
O Early weaning affects magnitude of
these changes but not the timing
Gastrin
O Gastrin interacts with its receptor to
regulate differentiation and proliferation of
epithelial cells in the small intestine.
O Gastrin increases ratios of:
O RNA:body weight
O Gut weight:body weight
O Protein:body weight
O Also increases DNA synthesis in intestinal
tissue
Gastrin
O Injection with exogenous pentagastrin:
O Within 1 hour, 50% increase in mRNA synthesis
O 2h later increase in protein synthesis (peaks
within 6 h)
O DNA synthesis maximized by 16 h
O Sharp increase in cellular oxygen
consumption associated with gastrin
action
O Oxygen may be a limiting factor in tissue
response to gastrin in fetus
Gastrin
O Receptors normally appear in rat at 18-
20 days of age
O Injection with corticosterone acetate in
7 day old pups results in premature
receptor appearance (by day 10)
O Adrenalectomy delays appearance of
gastrin receptors until day 25
O In rats, effects of corticosterone on gut
closure to macromolecular transport
may be mediated by gastrin
Gastrin
O No gastrin binding sites in small intestine
of normal piglets
O In piglet, other factors regulate small
intestinal development and growth
O In lab rat—binding sites appear at
weaning and gradually increase
Thyroid Hormone: T3, T4, rT3
O Thyroid gland
regulates metabolic
rate in different
tissues
O Iodothyronines
O Result from coupling
of two iodinated
tyrosine molecules
O Thyroxine (T3)
O Triiodothyronine (T4)
O Reverse T3 (rT3)
Thyroid Hormone
O Hypothalamus produces/releases thyroid
O
O
O
O
releasing hormone (TRH) to the pituitary
Pituitary releases thryroid stimulating
hormone
TSH stimulates T4 synthesis and release
from the thyroid
T4 monodeiodinated to T3 in peripheral
tissues
T3 provides negative feedback to TSH
Thyroid Hormone
O In humans, pituitary-thyroid axis is active
O
O
O
O
by 10-12 weeks of gestation
rT3 produced in excess to T3; function
unknown
4-6 days before birth—T3 increases, T4
and rT3 decrease
T3 continues to increase after birth
Maybe mediated by cortisol induced
increase in T4 to T3 interconversion
Thyroid Hormone
O Removal of thyroid prolongs gestation,
decreases body weight by 33%
O In the rat:
O T4 stimulates skeletal growth in neonatal
O
O
O
O
period (not juvenile period)
T4 /T3 ratio decreases 5d-12d
T4 production then increases, increasing
ratio at 14d
Return to adult values by 26d due to an
increase in production rate of T3
Correspond to changes in human fetus
during last trimester
Thyroid Hormone
O In bovine, T4 levels at birth twice that of
mature bovine
O By 6 days, approach normal adult values
O During first 24 hours, thyroid binding
globulin decreases more rapidly than T4
O Allows more T4 for metabolic uses during
crucial period when calf is adapting to
new environment
Cortisol
O Cortisol plays a permissive
role in general fetal growth
O Large portion of fetal
cortisol is of maternal origin
O Protein-bound forms are
physiologically inactive
O Corticosteroid binding
globulin (CBG)
concentration increases in
fetal sheep beginning at
day 75, decreases rapidly
after birth
Cortisol
O High corticosteroid levels on day of birth in
piglets
O Due to endogenous biosynthesis (not placental
transfer)
O Provide negative feedback against further
production—suppress ACTH production
O High glucocorticoid levels in calves associated
with stress at calving
O Correlated to degree of acidosis in calves at birth
O Cortisol concentrations 2.5 times higher in calf
than dam at birth
O Initially 12.1 g/dldecrease to 4.9 g/dl by 12h1.1
g/dl by 12 days
Cortisol
O Cortisol acts to prevent hypoglycemia
O Amplifies actions of glucagon and
epinephrine by building up glycogen
stores before hypoglycemic state occurs
O Major impact is on liver glycogen
O High cortisol leads to increases in plasma
glucose
O Antagonizes actions of insulin on glucose
metabolism
O Inhibits insulin-stimulated glucose uptake in
adipose and muscle tissue
O Reverses insulin suppression of hepatic
glucose production
Cortisol
O Decrease in cortisol concentration in
calves during first 12 hours
O Hemodilution effect (plasma volume
increases)
O Plasma corticosteroids are influenced by
feeding
O Immediate postprandial cortisol peak in first
few minutes after drinking milk
O Heart rate doubles, blood pressure increases
during drinking
O Plasma cortisol levels in calves 2-5 weeks
old similar to mature bovines (5 ng/dl)
Cortisol
O Cortisol concentrations at birth are:
O Positively correlated with increase in blood
glucose
O Inversely related to insulin
O Why?
O May indicate adrenal response to stress of
birth, new environment
O May be cause by increased activity of
sympathetic innervation to the liver
O Direct stimulation of glycogenolysis
Adrenocorticotropic Hormone
O Pituitary synthesizes adrenocorticotropin
hormone (ACTH)
O Abnormalities causing loss of pituitary or
adrenal function associated with small
effects on growth retardation
O ACTH interaction with receptor causes
activation of adenylate cyclase system,
increase in cAMP steroidogenesis
Adrenocorticotropic Hormone
O Adenylate cyclase more responsive to ACTH in
newborn rat adrenal glands than in late
gestation
O Receptor density unaltered
O Greater total number of receptors due to
increasing size of the adrenal gland
O Number of ACTH receptors/g DNA decreases
after birth
O Correlated with ACTH and cortisone plasma levels
O ACTH may upregulate its own receptor
O ACTH concentration increases in the sheep
fetus near term
O Not clearly related to cortisol levels
Growth Hormone
O In human fetus, GH is detected by 10 weeks
O
O
O
O
and reaches peak by 24 weeks
GH does not cross the placenta
In sheep, fetal pituitary is insensitive to
suppressant effects of somatostatin, leading
to high levels of fetal GH
GH secretion does not affect growth or
fetal IGF secretion—due to lack of GH
receptors in fetal tissues
Dramatic decrease in GH at birth suggests
negative feedback mechanisms to the
hypothalamus become functional
immediately following parturition
Growth Hormone
O GH dependent growth (postnatal)
O 3-12 months in humans
O 1-12 weeks in sheep
O 3 weeks in rat
O 15 weeks in rabbit
O Hypophysectomy does not affect
birthweight in rhesus monkeys
O Anencephalic fetus has near normal
growth rate despite low GH levels
Growth Hormone
O During neonatal period, GH more effective
stimulating tissue growth than skeletal
growth
O May stimulate cartilage growth and
differentiation during the neonatal period
O GH receptors throughout the GI tract of
the rat
O Suggests direct role for GH in gut growth
and/or differentiation
Growth Hormone
O GH high at birth in rat pups, declines with age
O High GHRH activity in rat milk stimulates GH
release after suckling
O GH concentrations are increased during active
suckling in rat pups—may also be because of
increased temperature
O GH feeds back to hypothalamus to inhibit
synthesis, release of GHRH in neonatal rats
O GH is NOT increased following colostrum
feeding in calves
Questions?