Neuroendocrinology

Hormones

Endocrine hormonesSecreted directly into the bloodControlled by pituitary (master gland)and hypothalamus

Exocrine HormonesSecreted into ducts

Not controlled by pituitary glandor hypothalamus (e.g., gut hormones)

Hormones

Neurotransmitters

long latency, long duration of effect (mins/days)

short latency, short duration of effect (msec)

delivered via blood

released directly onto target cells

diffuse actions

specific actions

released from endocrine cells

released from neurons

This distinction has become blurred; e.g.peptide neurotransmitters/neuromodulators,monoamines, etc.

Pituitary Gland(Hypophysis)

Anterior Pituitary(Adenohypophysis)

Posterior Pituitary(Neurohypophysis)

Endocrine Hormones`

Neurohypophysial hormonesOxytocinVasopressin

Adenohypophysial hormonesDirect Actions

ProlactinMelanocyte-stimulating hormone (MSH)

Somatotrophin (growth hormone; GH)

Indirect actions

Thyrotrophin (TSH)Corticotrophin (ACTH)

GonadotrophinsLuteinizing Hormone (LH)

Follicle-stimulating hormone (FSH)

Hypothalamus

Adenohypophysis

Endocrine Gland

Target tissues

Control of Adenohypophysial Hormones with Indirect

Actions

IndirectLoop

ShortLoop

DirectLoop

Releasing Factor

Trophic hormone

Endocrinehormone

All loops are negative feedback loops. Increases in the amount of the substances monitored reduces further secretion of those substances.

neural inputs

Indirect ActingACTH, TSH, LH, FSH

Hypothalamus

Adenohypophysis

Target tissues

Control of AdenohypophysialHormones withDirect Actions

IndirectLoop

Inhibitingfactor

DirectLoop

Releasing Factor

All loops are negative feedback loops. Increases in the amount of the substances monitored reduces further secretion of those substances.

neural inputs

Direct ActingGH, MSH, Prolactin

Direct ActingHormone

Endocrine HormonesAdenohypophysial hormones

Direct ActionsSomatotrophin (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 HormonesAdenohypophysial hormones

Direct Actions

ProlactinSomatotrophin (growth hormone; GH)

prolactin release inhibited by prolactin inhibiting factor (PIF)

PIF secretion inhibited by stimulation of nipples

stimulates milk production

Prolactin releasing factorprolactinmammaries

Endocrine HormonesAdenohypophysial hormones

Direct Actions

ProlactinMelanocyte-stimulating hormone (MSH)

Somatotrophin (growth hormone; GH)

MSH releasing factor melanocyte-stimulating hormonemelanocytes

stimulates melanin synthesisin melanocytes

Hypothalamus

Adenohypophysis

Endocrine Gland

Target tissues

Control ofAdrenocortical Hormones

IndirectLoop

ShortLoop

DirectLoop

Corticotrophin(ACTH)

Cortisol andAldosterone

neural inputs

CRF

Endocrine HormonesAdenohypophysial hormones

Direct Actions

ProlactinMelanocyte-stimulating hormone (MSH)

Somatotrophin (growth hormone; GH)

Indirect actionsCorticotrophin (ACTH) regulates stress hormones and nutrient utilization (glucocorticoids) and water/mineral balance (mineralocorticoids)

Endocrine HormonesAdenohypophysial hormones

Direct Actions

ProlactinMelanocyte-stimulating hormone (MSH)

Somatotrophin (growth hormone; GH)

Indirect actionsCorticotrophin (ACTH)

Corticotrophin releasing factor (CRF) ===> corticotrophin ===> cortisol, aldosterone ===> tissues

cortisol inhibits protein synthesisstimulates gluconeogenesis(synthesis of glucose from proteins)inhibits conversion of carbohydrates to fats

aldosterone regulates electrolytes,especially sodium

principal stress hormonephysiological stress—challenges to homeostasispsychological stress—perceived challenges limbic system participation

Corticotrophin

Controls secretions from adrenal cortexad = 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 arestress-related

What is stress?

What is stress?It is “a real or interpreted threatto the physiological orpsychological integrity of anindividual that results inphysiological and/or behavioralresponses. In biomedicine,stress often refers to situationsin which adrenal glucocorticoidsand 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 stress1. Systemic stress

physiological threat

2. Processive stress potential or eventual threat

In adults, responses to processive, but not systemic,stress is blocked by lesions ofthe hippocampus

Systemic stress is also referred to asphysiological stress, and processivestress is oten referred to as psychological stress

Endocrine HormonesAdenohypophysial hormones

Direct Actions

ProlactinMelanocyte-stimulating hormone (MSH)

Somatotrophin (growth hormone; GH)

Indirect actions

Thyrotrophin (TSH)Corticotrophin (ACTH)

Thyrotrophin releasing factor (TRF or TRH) thyrotrophin (TSH) thyroid gland thyroxine tissues

regulates development

regulates metabolic rate in adulthood

Hypothalamus

Adenohypophysis

Thyroid Gland

Target tissues

Control ofThyroid Hormones

IndirectLoop

ShortLoop

DirectLoop

TRF (TRH)

TSH

Thyroxine (T4)

neural inputs

Thyroid Hormones asRegulators of Development

Stimulation of Metamorphosisin Amphibians

iin brain, thyroid hormones stimulatesecondary neurogenesis of cerebellarPurkinje cells, development of optic tectum

e.g. loss of gills, septation of lungs remodeling of gastrointestinal tract loss of tail, growth of limbs

Thus, thyroxine stimulates both cell loss (apoptosis) and cell proliferation (mitosis) in different populations

Thyroid Hormones asRegulators of Development

Thus, thyroxine stimulates both cell loss (apoptosis) and cell proliferation (mitosis) in different populations.

This role contrasts with that of growthhormone.

In the absence of growth hormone, tadpoles still undergo metamorphosisbut have reduced size.

In the absence of thyroxine, tadpolescontinue to grow but fail to transform.

Analogous Effectsare seen in mammals

In mammals, growth hormone deficiencyresults in dwarfism; thyroid hormonedeficiency results in cretinism.

Dwarves reach developmental milestonesat the normal time; they are simply of shorter stature.

Hypothyroid individuals are also small,but more profoundly, developmentalmilestones are greatly delayed.

15-20 years old,Congo-Kinshasa

Endocrine HormonesAdenohypophysial hormones

Direct Actions

ProlactinMelanocyte-stimulating hormone (MSH)

Somatotrophin (growth hormone; GH)

Indirect actions

Thyrotrophin (TSH)Corticotrophin (ACTH)

GonadotrophinsGonadotrophin releasing hormone (GnRH) orLeuteinizing hormone releasing hormone (LHRH) luteinizing hormone (LH) and

follicle stimulating hormone (FSH) gonads (ovaries or testes) estrogen and progesterone

or androgens tissues

organizational effectsactivational effects

Definitions of Sex

Genetic (XX vs XY

Gonadal (ovaries vs testes)

Hormonal (cyclic vs constant releaseMorphological (clitoris, labia vs penis, scrotum)

Behavioral (gender role behavior)

Identity (what you consider yourself to be)

Hypothalamus

Adenohypophysis

Testes (♂)Ovaries (♀)

Target tissues

(GnRH)

Luteinizing Hormone (LH)Follicle Stimulating Hormone (FSH)

Testosterone (♂)Estrogen/Progesterone (♀)

Control ofSex Hormones

neural inputs

Sexual DimorphismsPhenotypic differencesbetween males and females

They can be:anatomicalphysiologicalbehavioralcognitive

They can be:qualitativequantitative

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 differentiateinto tissues typical of either sex

Bipotential tissues: Undifferentiated tissuethat can differentiate into either a male orfemale form.

Sexual Dimophisms: Structures, functionsor behaviors that differ qualitatively or quantitatively between the sexes.

Castrate male hamster at birth

Prototypical Experiment(Males)

(before period of brain differentiation)

Test in adulthood

place with receptive female

inject with testosterone

male typical behavior low

mounting, intromission (ejaculation not possible)

female-typical behavior high

darting, ear-wiggling, lordosis

place with male

inject with estrogen and progesterone

Neuter female hamster at birth andinject with testosterone

Prototypical Experiment(Females)

(before period of brain differentiation)

Test in adulthood

place with receptive femaleinject with testosterone

male typical behavior high (mounting)

female-typical behavior low (ear-wiggling, darting, lordosis)

place with male

inject with estrogen and progesterone

Differentiation of the Brain

MasculinizationInduction of male characteristics paradoxically, dependent on estradiol

DefeminizationSuppression of female characteristics

Two processes both are dependent of fetal androgens

estrodiol

aromatase 5-alphareductase

cholesterol

DHT

Why aren’t all femalesmasculinized?

α-fetoproteinbinds to estradiol extracellularyand 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 thattestosterone be secreted from the fetal testes during a sensitive period of development. Masculinization and defeminization of the brain requires theconversion of testosterone to estradiol byneurons of the brain. Masculinization ofperipheral tissues requires conversion oftestosterone to dihydrotestosterone (DHT).

Sexual DimorphismsPhenotypic differencesbetween males and females

They can be:anatomicalphysiologicalbehavioralcognitive

They can be:qualitativequantitiave

estrodiol

aromatase 5-alphareductase

cholesterol

DHT

XX Congenital Adrenal Hyperplasia (CAH)

XX Congenital Adrenal Hyperplasia (CAH)

estrodiol

aromatase 5-alphareductase

cholesterol

DHT

Female Spotted Hyena

estrodiol

aromatase 5-alphareductase

cholesterol

DHT

estrodiol

aromatase 5-alphareductase

cholesterol

DHT

Endocrine HormonesAdenohypophysial hormones

Direct Actions

ProlactinMelanocyte-stimulating hormone (MSH)

Somatotrophin (growth hormone; GH)

Indirect actions

Thyrotrophin (TSH)Corticotrophin (ACTH)

Gonadotrophins

LH and FSH stimulate ovulation in females and spermatogenesis in males

Gonadotrophin releasing hormone (GnRH) orLeuteinizing 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 andactivate gender-typical behavior

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)

Correspondto MPOA of rodents

Endocrine Hormones

Neurohypophysial hormonesOxytocin

Adenohypophysial hormonesDirect Actions

ProlactinMelanocyte-stimulating hormone (MSH)

Somatotrophin (growth hormone; GH)

Indirect actions

Thyrotrophin (TSH)Corticotrophin (ACTH)

GonadotrophinsLuteinizing Hormone (LH)

Follicle-stimulating hormone (FSH)

stimulation of cervix, nipples ===> oxytocin

primes maternal behavior

stimulates milk ejection

Endocrine Hormones

Neurohypophysial hormonesOxytocin

Vasopressin

Adenohypophysial hormonesDirect Actions

ProlactinMelanocyte-stimulating hormone (MSH)

Somatotrophin (growth hormone; GH)

Indirect actions

Thyrotrophin (TSH)Corticotrophin (ACTH)

GonadotrophinsLuteinizing Hormone (LH)

Follicle-stimulating hormone (FSH)

low blood pressure vasopressin (ADH)

kidneys retain more water

Endocrine Hormones

Neurohypophysial hormonesOxytocinVasopressin

Adenohypophysial hormonesDirect Actions

ProlactinMelanocyte-stimulating hormone (MSH)

Somatotrophin (growth hormone; GH)

Indirect actions

Thyrotrophin (TSH)Corticotrophin (ACTH)

GonadotrophinsLuteinizing Hormone (LH)

Follicle-stimulating hormone (FSH)