1. Neuroendocrinology

2. Hormones Endocrine hormones Exocrine 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)

3. Hormones Neurotransmitters 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.

4. Pituitary Gland (Hypophysis) Anterior Pituitary (Adenohypophysis)
Posterior Pituitary
(Neurohypophysis)

7. 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

8. Control of Adenohypophysial Hormones with Indirect Actions
neural inputs
Hypothalamus
Indirect
Loop
Short
Loop
Releasing
Factor
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.

9. Control of Adenohypophysial Hormones withDirect Actions
neural inputs
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.

11. 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

12. 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

13. 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

14. Adrenocortical Hormones
Control of
Adrenocortical Hormones
neural inputs
Hypothalamus
Indirect
Loop
Short
Loop
CRF
Adenohypophysis
Corticotrophin
(ACTH)
Direct
Loop
Endocrine Gland
Cortisol and
Aldosterone
Target tissues

15. 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)

16. 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

17. Corticotrophin Controls secretions from adrenal cortex
ad = on, renal = kidney, so
adrenal = on the kidney

18. 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

19. What is stress?

20. 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.

21. What is stress? Is it a subjective experience?
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

22. 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

23. 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

24. Control of Thyroid Hormones
neural inputs
Hypothalamus
Indirect
Loop
Short
Loop
TRF (TRH)
Adenohypophysis
TSH
Direct
Loop
Thyroid Gland
Thyroxine (T4)
Target tissues

25. Regulators of Development
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

26. Regulators of Development
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.

27. 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.

28. 15-20 years old,
Congo-Kinshasa

30. 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

31. 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)

32. Control of Sex Hormones
Hypothalamus
neural inputs
(GnRH)
Adenohypophysis
Luteinizing Hormone (LH)
Follicle Stimulating Hormone (FSH)
Testes (♂)
Ovaries (♀)
Testosterone (♂)
Estrogen/Progesterone (♀)
Target tissues

33. Sexual Dimorphisms Phenotypic differences between males and females
They can be:
anatomical
physiological
behavioral
cognitive
They can be:
qualitative
quantitative

34. Effects of Sex Hormones
Organizational Effects
structural
sensitive period
irreversible
masculinization/defeminization
Activational Effects
act on existing structure
no sensitive period
reversible

36. Bipotential tissues—those that can differentiate
into tissues typical of either sex

37. 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.

38. 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

39. 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)

40. 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

41. estrodiol
aromatase
5-alpha
reductase
cholesterol
DHT

42. Why aren’t all females masculinized? α-fetoprotein
binds to estradiol extracellulary
and prevents entry into cell

44. ♂ ♁ medial preoptic area (MPOA)
= “the” sexually dimorphic nucleus (SDN)

46. 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).

47. Sexual Dimorphisms Phenotypic differences between males and females
They can be:
anatomical
physiological
behavioral
cognitive
They can be:
qualitative
quantitiave

48. estrodiol
aromatase
5-alpha
reductase
cholesterol
DHT

49. XX Congenital Adrenal Hyperplasia (CAH)

50. XX Congenital Adrenal Hyperplasia (CAH)

51. estrodiol
aromatase
5-alpha
reductase
cholesterol
DHT

52. Female Spotted Hyena

53. estrodiol
aromatase
5-alpha
reductase
cholesterol
DHT

55. estrodiol
aromatase
5-alpha
reductase
cholesterol
DHT

57. 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

58. 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.

59. Gladue, Green & Hellman,(1983),
Science, 225,

60. ♂ ♁ medial preoptic area (MPOA)
= “the” sexually dimorphic nucleus (SDN)

61. Correspond
to MPOA of rodents

64. Endocrine Hormones Adenohypophysial hormones Neurohypophysial 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

65. Endocrine Hormones Adenohypophysial hormones Neurohypophysial 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

66. Endocrine Hormones Adenohypophysial hormones Neurohypophysial 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