Transcript Hormones, the brain and behavior

Neuroendocrinology
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)
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.
Pituitary Gland
(Hypophysis)
Anterior Pituitary
(Adenohypophysis)
Posterior Pituitary
(Neurohypophysis)
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
Control of Adenohypophysial
Hormones with Indirect Actions
neural inputs
Indirect
Loop
Hypothalamus
Short
Loop
Releasing
Factor
Adenohypophysis
Direct
Loop
Indirect Acting
ACTH, TSH,
LH, FSH
Trophic
hormone
Endocrine Gland
Endocrine
hormone
Target tissues
All loops are negative feedback loops.
Increases in the amount of the substances monitored
reduces further secretion of those substances.
Control of Adenohypophysial
Hormones withDirect Actions
neural inputs
Indirect
Loop
Hypothalamus
Inhibiting
factor
Releasing
Factor
Adenohypophysis
Direct
Loop
Direct Acting
GH, MSH,
Prolactin
Direct
Acting
Hormone
Target tissues
All loops are negative feedback loops.
Increases in the amount of the substances monitored
reduces further secretion of those substances.
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
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
Endocrine Hormones
Adenohypophysial hormones
Direct Actions
Somatotrophin (growth hormone; GH)
Prolactin
Melanocyte-stimulating hormone (MSH)
MSH releasing factor
 melanocyte-stimulating hormonemelanocytes
stimulates melanin synthesis
in melanocytes
Control of
Adrenocortical Hormones
neural inputs
Hypothalamus
Indirect
Loop
Short
Loop
CRF
Adenohypophysis
Direct
Loop
Corticotrophin
(ACTH)
Endocrine Gland
Cortisol and
Aldosterone
Target tissues
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)
Endocrine Hormones
Adenohypophysial hormones
Direct Actions
Somatotrophin (growth hormone; GH)
Prolactin
Melanocyte-stimulating hormone (MSH)
Indirect actions
Corticotrophin (ACTH)
Corticotrophin releasing factor (CRF)
===> corticotrophin
===> cortisol, aldosterone
===> tissues
cortisol inhibits protein synthesis
stimulates gluconeogenesis
(synthesis of glucose from proteins)
inhibits conversion of carbohydrates to fats
principal stress hormone
physiological stress—challenges to homeostasis
psychological stress—perceived challenges
limbic system participation
aldosterone regulates electrolytes,
especially sodium
Corticotrophin
Controls secretions from adrenal cortex
ad = on, renal = kidney, so
adrenal = on the kidney
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
What is stress?
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.
What is stress?
Is it a demanding stimulus or
situation?
“I’m under a lot of stress.”
Is it a subjective experience?
“I’m feeling stressed out.”
depression
Is it a physiological challenge?
hunger, thirst, fatigue
Is it an endocrine response?
circulating stress hormones
Two types of stress
1. 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
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
Control of
Thyroid Hormones
neural inputs
Hypothalamus
Indirect
Loop
Short
Loop
TRF (TRH)
Adenohypophysis
Direct
Loop
TSH
Thyroid Gland
Thyroxine (T4)
Target tissues
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
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.
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.
15-20 years old,
Congo-Kinshasa
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
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)
Control of
Sex Hormones
Hypothalamus
neural inputs
(GnRH)
Adenohypophysis
Luteinizing Hormone (LH)
Follicle Stimulating Hormone (FSH)
Testes (♂)
Ovaries (♀)
Testosterone (♂)
Estrogen/Progesterone (♀)
Target tissues
Sexual Dimorphisms
Phenotypic differences
between males and females
They can be:
anatomical
physiological
behavioral
cognitive
They can be:
qualitative
quantitative
Effects of Sex
Hormones
• Organizational Effects
•
•
•
•
structural
sensitive period
irreversible
masculinization/defeminization
• Activational Effects
• act on existing structure
• no sensitive period
• reversible
Bipotential tissues—those that can differentiate
into tissues typical of either sex
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.
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
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)
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
cholesterol
aromatase
estrodiol
5-alpha
reductase
DHT
Why aren’t all females
masculinized?
α-fetoprotein
binds to estradiol extracellulary
and prevents entry into cell
♁
♂
medial preoptic area (MPOA)
= “the” sexually dimorphic nucleus (SDN)
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).
Sexual Dimorphisms
Phenotypic differences
between males and females
They can be:
anatomical
physiological
behavioral
cognitive
They can be:
qualitative
quantitiave
cholesterol
aromatase
estrodiol
5-alpha
reductase
DHT
XX Congenital Adrenal Hyperplasia (CAH)
XX Congenital Adrenal Hyperplasia (CAH)
cholesterol
aromatase
estrodiol
5-alpha
reductase
DHT
Female Spotted Hyena
cholesterol
aromatase
estrodiol
5-alpha
reductase
DHT
cholesterol
aromatase
estrodiol
5-alpha
reductase
DHT
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
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.
Gladue, Green & Hellman,(1983),
Science, 225, 1496-1499.
♁
♂
medial preoptic area (MPOA)
= “the” sexually dimorphic nucleus (SDN)
Correspond
to MPOA of
rodents
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
===> oxytocin
primes maternal behavior
stimulates milk ejection
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
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