Neuroendocrinology

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Neuroendocrinology
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Hormones
Endocrine hormones
Secreted directly into the blood
Controlled by pituitary (master gland) and
hypothalamus
Exocrine Hormones
Secreted into ducts
Not controlled by pituitary gland or hypothalamus
(e.g., gut hormones)
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Hormones
released from endocrine cells
long latency, long duration of effect (mins/days)
delivered via blood
diffuse actions
Neurotransmitters
released from neurons
short latency, short duration of effect (msec)
released directly onto target cells
specific actions
This distinction has become blurred e.g. peptide
neurotransmitters/neuromodulators, monoamines,
etc.
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Pituitary Gland
(Hypophysis)
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Endocrine Hormones
Adenohypophysial hormones
Direct Actions
Somatotrophin (growth hormone GH)
Prolactin
Melanocyte-stimulating hormone (MSH)
Indirect actions
Corticotrophin (ACTH)
Thyrotrophin (TSH)
Gonadotrophins
Luteinizing Hormone (LH)
Follicle-stimulating hormone (FSH)
Neurohypophysial hormones
Oxytocin
Vasopressin
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Control of Adenohypophysial Hormones with
Indirect Actions
Hypothalamus
Short Loop
Releasing Factor
Indirect Loop
Adenohypophysis
Trophic hormone
Direct Loop
Endocrine Gland
Endocrine hormone
Indirect Acting ACTH, TSH, LH, FSH
Target tissues
All loops are negative feedback loops.
Increases in the amount of the substances
monitored reduces further secretion of those
substances.
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Control of Adenohypophysial Hormones withDirect
Actions
Hypothalamus
Indirect Loop
Inhibiting factor
Releasing Factor
Adenohypophysis
Direct Loop
Direct Acting Hormone
Direct Acting GH, MSH, Prolactin
Target tissues
All loops are negative feedback loops.
Increases in the amount of the substances
monitored reduces further secretion of those
substances.
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Endocrine Hormones
Adenohypophysial hormones
Direct Actions
Somatotrophin (growth hormone GH)
Growth hormone releasing hormone (GHRH) ?
somatotrophin (GH) ? somatic tissues
promotes growth by stimulating proteins
synthesis of virtually all tissues
GH release inhibited by somatostatin
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Endocrine Hormones
Adenohypophysial hormones
Direct Actions
Somatotrophin (growth hormone GH)
Prolactin
Prolactin releasing factor? prolactin?mammaries
stimulates milk production
prolactin release inhibited by prolactin
inhibiting factor (PIF)
PIF secretion inhibited by stimulation of nipples
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Endocrine Hormones
Adenohypophysial hormones
Direct Actions
Somatotrophin (growth hormone GH)
Prolactin
Melanocyte-stimulating hormone (MSH)
MSH releasing factor ? melanocyte-stimulatin
g hormone?melanocytes
stimulates melanin synthesis in melanocytes
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Control of Adrenocortical Hormones
Hypothalamus
Indirect Loop
Short Loop
CRF
Adenohypophysis
Corticotrophin (ACTH)
Direct Loop
Endocrine Gland
Cortisol and Aldosterone
Target tissues
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Endocrine Hormones
Adenohypophysial hormones
Direct Actions
Somatotrophin (growth hormone GH)
Prolactin
Melanocyte-stimulating hormone (MSH)
Indirect actions
Corticotrophin (ACTH) regulates stress
hormones and nutrient utilization
(glucocorticoids) and water/mineral balance
(mineralocorticoids)
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Endocrine Hormones
Adenohypophysial hormones
Direct Actions
Somatotrophin (growth hormone GH)
Prolactin
Melanocyte-stimulating hormone (MSH)
Indirect actions
Corticotrophin (ACTH)
Corticotrophin releasing factor (CRF) gt
corticotrophin gt cortisol, aldosterone
gt tissues
cortisol inhibits protein synthesis stimulates
gluconeogenesis (synthesis of glucose from
proteins) inhibits conversion of carbohydrates to
fats
principal stress hormone physiological
stresschallenges to homeostasis psychological
stressperceived challenges limbic system
participation
aldosterone regulates electrolytes, especially
sodium
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Corticotrophin
Controls secretions from adrenal cortex ad on,
renal kidney, so adrenal on the kidney
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the adrenal gland is really two glands in one
cortex bark, medulla core medulla is a
modified sympathetic ganglion cortex is an
endocrine gland Activity of both medulla and
cortex are stress-related
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What is stress?
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What is stress?
It is a real or interpreted threat to the
physiological or psychological integrity of
an individual that results in physiological
and/or behavioral responses. In
biomedicine, stress often refers to situations in
which adrenal glucocorticoids and catecholamines
are elevated because of an experience. McEwen,
B. (2000) In G. Fink (Ed.) Encyclopedia of
Stress, Vol. 3. San Diego Academic Press.
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What is stress?
Is it a demanding stimulus or situation? Im
under a lot of stress. Is it a subjective
experience? Im feeling stressed
out. depression Is it a physiological
challenge? hunger, thirst, fatigue Is it an
endocrine response? circulating stress hormones
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Two types of stress

• Systemic stress
• physiological threat
• 2. Processive stress
• potential or eventual threat

In adults, responses to processive, but not
systemic, stress is blocked by lesions of the
hippocampus
Systemic stress is also referred to
as physiological stress, and processive stress is
oten referred to as psychological stress
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Endocrine Hormones
Adenohypophysial hormones
Direct Actions
Somatotrophin (growth hormone GH)
Prolactin
Melanocyte-stimulating hormone (MSH)
Indirect actions
Corticotrophin (ACTH)
Thyrotrophin (TSH)
Thyrotrophin releasing factor (TRF or TRH) ?
thyrotrophin (TSH) ? thyroid gland ?
thyroxine ? tissues
regulates development
regulates metabolic rate in adulthood
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Control of Thyroid Hormones
Hypothalamus
Indirect Loop
Short Loop
TRF (TRH)
Adenohypophysis
TSH
Direct Loop
Thyroid Gland
Thyroxine (T4)
Target tissues
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Thyroid Hormones as Regulators of Development
Stimulation of Metamorphosis in Amphibians
e.g. loss of gills, septation of lungs
remodeling of gastrointestinal tract loss of
tail, growth of limbs
iin brain, thyroid hormones stimulate secondary
neurogenesis of cerebellar Purkinje cells,
development of optic tectum
Thus, thyroxine stimulates both cell loss
(apoptosis) and cell proliferation (mitosis) in
different populations
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Thyroid Hormones as Regulators of Development
Thus, thyroxine stimulates both cell loss
(apoptosis) and cell proliferation (mitosis) in
different populations.
This role contrasts with that of
growth hormone. In the absence of growth
hormone, tadpoles still undergo
metamorphosis but have reduced size. In the
absence of thyroxine, tadpoles continue to grow
but fail to transform.
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Analogous Effects are seen in mammals
In mammals, growth hormone deficiency results in
dwarfism thyroid hormone deficiency results in
cretinism.
Dwarves reach developmental milestones at the
normal time they are simply of shorter stature.
Hypothyroid individuals are also small, but more
profoundly, developmental milestones are greatly
delayed.
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15-20 years old, Congo-Kinshasa
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Endocrine Hormones
Adenohypophysial hormones
Direct Actions
Somatotrophin (growth hormone GH)
Prolactin
Melanocyte-stimulating hormone (MSH)
Indirect actions
Corticotrophin (ACTH)
Thyrotrophin (TSH)
Gonadotrophins
Gonadotrophin releasing hormone (GnRH)
or Leuteinizing hormone releasing hormone (LHRH)
?luteinizing hormone (LH) and follicle
stimulating hormone (FSH) ?gonads (ovaries
or testes) ?estrogen and progesterone or
androgens ?tissues
organizational effects
activational effects
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Definitions of Sex
Genetic (XX vs XY
Gonadal (ovaries vs testes)
Hormonal (cyclic vs constant release
Morphological (clitoris, labia vs penis, scrotum)
Behavioral (gender role behavior)
Identity (what you consider yourself to be)
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Control of Sex Hormones
Hypothalamus
neural inputs
(GnRH)
Adenohypophysis
Luteinizing Hormone (LH) Follicle Stimulating
Hormone (FSH)
Testes (?) Ovaries (?)
Testosterone (?) Estrogen/Progesterone (?)
Target tissues
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Sexual Dimorphisms
Phenotypic differences between males and females
They can be anatomical physiological behaviora
l cognitive
They can be qualitative quantitative
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Effects of Sex Hormones

• Organizational Effects
• structural
• sensitive period
• irreversible
• masculinization/defeminization
• Activational Effects
• act on existing structure
• no sensitive period
• reversible

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Bipotential tissuesthose that can
differentiate into tissues typical of either sex
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Bipotential tissues Undifferentiated
tissue that can differentiate into either a male
or female form.
Sexual Dimophisms Structures, functions or
behaviors that differ qualitatively or
quantitatively between the sexes.
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Prototypical Experiment (Males)
Castrate male hamster at birth
(before period of brain differentiation)
Test in adulthood
inject with testosterone
place with receptive female
male typical behavior low
mounting, intromission (ejaculation not possible)
inject with estrogen and progesterone
place with male
female-typical behavior high
darting, ear-wiggling, lordosis
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Prototypical Experiment (Females)
Neuter female hamster at birth and inject with
testosterone
(before period of brain differentiation)
Test in adulthood
inject with testosterone
place with receptive female
male typical behavior high (mounting)
inject with estrogen and progesterone
place with male
female-typical behavior low (ear-wiggling,
darting, lordosis)
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Differentiation of the Brain
Two processes both are dependent of fetal
androgens
Masculinization
Induction of male characteristics
paradoxically, dependent on estradiol

Defeminization
Suppression of female characteristics
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Why arent all females masculinized?
a-fetoprotein binds to estradiol
extracellulary and prevents entry into cell
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?
?
medial preoptic area (MPOA) the sexually
dimorphic nucleus (SDN)
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Sexual Differentiation
Female is the default sex no sex hormones are
required for normal organization of the brain or
peripheral tissues.
Male development requires that testosterone be
secreted from the fetal testes during a
sensitive period of development.
Masculinization and defeminization of the brain
requires the conversion of testosterone to
estradiol by neurons of the brain.
Masculinization of peripheral tissues requires
conversion of testosterone to dihydrotestosterone
(DHT).
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Sexual Dimorphisms
Phenotypic differences between males and females
They can be anatomical physiological behaviora
l cognitive
They can be qualitative quantitiave
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XX Congenital Adrenal Hyperplasia (CAH)
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XX Congenital Adrenal Hyperplasia (CAH)
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Female Spotted Hyena
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Endocrine Hormones
Adenohypophysial hormones
Direct Actions
Somatotrophin (growth hormone GH)
Prolactin
Melanocyte-stimulating hormone (MSH)
Indirect actions
Corticotrophin (ACTH)
Thyrotrophin (TSH)
Gonadotrophins
Gonadotrophin releasing hormone (GnRH)
or Leuteinizing hormone releasing hormone (LHRH)
? luteinizing hormone (LH) and follicle
stimulating hormone (FSH) ?gonads (ovaries
or testes) ? estrogen and progesterone or
androgens ?tissues
Testosterone masculinizes and defeminizes fetus
Produce secondary sex characteristics
and activate gender-typical behavior
LH and FSH stimulate ovulation in females and
spermatogenesis in males
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1. LH and FSH stimulate follicular development
2. Developing follicles secrete estrodiol
3. Increasing estrodiol stimulates GnRH release
4. LH surge stimulates ovulatoin
5. Luteinized cells secrete estradiol,
progesterone
6. Luteinized cells degenerate.
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Gladue, Green Hellman,(1983), Science, 225,
1496-1499.
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?
?
medial preoptic area (MPOA) the sexually
dimorphic nucleus (SDN)
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Correspond to MPOA of rodents
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Endocrine Hormones
Adenohypophysial hormones
Direct Actions
Somatotrophin (growth hormone GH)
Prolactin
Melanocyte-stimulating hormone (MSH)
Indirect actions
Corticotrophin (ACTH)
Thyrotrophin (TSH)
Gonadotrophins
Luteinizing Hormone (LH)
Follicle-stimulating hormone (FSH)
Neurohypophysial hormones
Oxytocin
stimulation of cervix, nipples gt oxytocin
primes maternal behavior
stimulates milk ejection
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Endocrine Hormones
Adenohypophysial hormones
Direct Actions
Somatotrophin (growth hormone GH)
Prolactin
Melanocyte-stimulating hormone (MSH)
Indirect actions
Corticotrophin (ACTH)
Thyrotrophin (TSH)
Gonadotrophins
Luteinizing Hormone (LH)
Follicle-stimulating hormone (FSH)
Neurohypophysial hormones
Oxytocin
Vasopressin
low blood pressure ? vasopressin (ADH)
kidneys retain more water
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Endocrine Hormones
Adenohypophysial hormones
Direct Actions
Somatotrophin (growth hormone GH)
Prolactin
Melanocyte-stimulating hormone (MSH)
Indirect actions
Corticotrophin (ACTH)
Thyrotrophin (TSH)
Gonadotrophins
Luteinizing Hormone (LH)
Follicle-stimulating hormone (FSH)
Neurohypophysial hormones
Oxytocin
Vasopressin