Neuroendocrinology Flashcards
Describe Berthold’s experiement
Studied chickens in 1849
Group 1: Castrated before adulthood
Group 2: Castrated, autotransplant
Group 3: Castrated, heterotransplant
Groups 2 and 3, new vascular supply and normal development
Group 1, no mating or fighting, smaller body
Conclusions:
1. Testes can be transplanted
2. Transplanted testes can function and produce sperm
3. Nerves are not necessary for testicular function (were cut)
New hypothesis: Testes make “secretory blood-born product”
Strengths: Easy to measure DV, used auto and heterotransplant
Weakness: no control group (sham operation)
Describe Young’s experiement
Guinea pig sexual behavior in 1959
Adult males show mounting with testosterone (T) manipulations
- Adult females do not respond to T manipulations; lordosis
Hypothesis: Hormonal events early in development are important for reproductive behaviors as adults
- Gave T or oil (control) to pregnant guinea pigs
- All female pups had their ovaries remove and given estradiol and progesterone as adults
Ovaries removed + Prenatal T = reduced lordosis and increased mounting
- Testes removed + T = decreased mounting
- Testes removed + estradiol + progesterone = lordosis
What are hormones?
Chemical secreted by cells in one part of the body and conveyed by blood to influence other cells for long lasting changes
What do protein and peptide hormones do?
Attach to membrane receptors and activate a second messenger within a cell
ex. GnRH, CRH, ACTH, insulin
Autocrine mediation
The same cell/cell type that secreted the hormone is effected
Paracrine mediation
Cells secrete chemicals that affect adjacent cells
Endocrine mediation
Secrete into bloodstream and target distant cells
Ectocrine mediation
i.e pheromones are released into the air and affect other animals
Monoamines
Made from 1 amino acid
ex. Epinephrine (adrenal), melatonin (pineal), dopamine (adrenal)
Lipid based hormones
ex. Prostaglandins
Steroids
Made by enzymes from cholesterol
ex. Glucocorticoids, androgens, estrogens progestins
Describe the effect of steroids
- Bind to membrane receptors exerting rapid effects
- Enter the cells and activate certain kinds of proteins in the cytoplasm
- Bind to receptors that bind to chromosomes to activate or inactivate genes
How do hormones affect behaviour?
Hormones can effect sensory systems, CNS (signal processing), motor response
Behaviour can effect hormone secretion
- Bidirectional
Describe the General Adaptation Syndrome
Hans Selye and stress:
- Stress is the non specific response to the body to any demand made upon it and is due to the adrenal glands 1. Alarm/initial stage 2. Resistance 3. Exhaustion
Describe the Alarm stage of GAS
- Adrenal glands release epinephrine, thus stimulating the sympathetic nervous system
- Also release cortisol, increasing blood glucose to provide extra energy
- Releases aldosterone; important for maintaining blood salt and volume
Describe the Resistance stage of GAS
- Sympathetic response declines, but continues to release cortisol
- Decrease activity to maintain state
Describe the exhaustion stage of GAS
- Individual is tired, inactive and vulnerable
- The nervous system and immune system no longer have the energy to sustain a response
HPA axis
Acts more slowly than the sympathetic nervous system, but dominates the response to prolonged stressors
Hypothalamus → CRH → Anterior pituitary → ACTH → Adrenal cortex → Cortisol + DHEA
How do cortisol and DHEA work
- Cortisol and DHEA act in opposition
Role of adrenal glands
In HPA axis
Progesterone → Corticosterone → Aldosterone
→ Cortisol
Adrenal medulla
On inside of adrenal gland
Secretes adrenomedullary hormone
Adrenal cortex
Where steroids are produced
On outside of adrenal gland
Effects of glucorticoids take longer but last longer
Contains:
Zona glomerulosa + Zona fasciculata +Zona reticularis
Zona glomerolosa
Secretes aldosterone: Mineral balance
Zona fasiculata
Secretes corticosterone and cortisol (glucorticoids)
Mobilize glucose + Suppress of immune system
Zona reticularis
Secretes DHEA
adrenomedullary hormone
Secretes monoamines and catecholamines from tyrosine
ex. Epinephrine, norepinephrine, dopamine
Male/Female Hormones
Testes produce more androgens than ovaries, and ovaries produce more estrogen, adrenal glands produce both
Males: aromatase in the brain, progesterone in the blood, and a local production of estradiol from plasma testosterone
Females: synthesize androgens in ovaries (precursors to estradiol), testosterone and androgens in the blood and aromatase in the brain
HPG axis males
Hypothalamus → GnRH, GnIH → Anterior pituitary → LH, FSH → testes → regulates gamete and sperm production and testosterone
Testes
- Produce androgens that increase the growth of the tests, causing them to produce more androgens (positive feedback)
- Produce Mullerian-inhibiting hormone (MIH) that causes Mullerian ducts to degenerate
Contains leydig calls and seminiferous tubules
Leydig cells
Located between seminiferous tubules
- Contains all the enzymes to make testosterone from cholesterol
Seminiferous tubules
Where sperm is made
GnRH in cichid fish
2 types of males; territorial and non territorial determined by their social environment during development and adulthood which regulates appearance, behaviour, growth and reproduction
Territorial fish: large GnRH neurons
- Get smaller + testes shrink + no reproduction if they are placed in an environment where they become non territorial (ie. they are no longer the biggest)
Non territorial fish: small GnRH neurons
- Get larger if they are put in an environment and become territorial
GnRH mRNA gene express in cichid fish
In preoptic area:
- See mRNA with in situ hybridization
- Neurons are larger in territorial fish than non territorial fish, with more GnRH present in territorial fish
Use PCR to quantify how much mRNA is in a region
Testosterone
- Differentiation of external genitals depends on testosterone levels (high=male)
- Testosterone → dihydrotestosterone
- High = tubercle grows into penis and scrotum develops
- Low = tubercle grows into clitoris and labia develops
Promotes male patterns and inhibits female patterns in early development
Part of negative feedback system
HPG axis females
GnRH → Anterior pituitary → LH + FSH → Ovary → Estradiol
- Estradiol is used in negative feedback but used in positive feedback during mentration
Ovaries
- Primary follicle is not developed
- Mature follicle is about to be release
Contains Theca cells + Granulosa cells - If ovum is fertilized → corpus leteum
- Produces progesterone to promote pregnancy
Theca cells
Produce androgens
Granulosa cells
Androgens → estradiol + estrogen using aromatase
Hypothalamus + Hormones
Releases small peptide hormones into the local blood system → regulate anterior pituitary
- eg. GnRH, CRH, GHRH
Transports peptides directly to posterior pituitary through axons → secreted into systemic blood system
Posterior Pituitary
- Made of neural tissue
- Neurons in the hypothalamus synthesize oxytocin (OT) and arginine vasopressin (AVP), posterior pituitary releases them
- Cell bodies (paraventricular and supraoptic nucleus) have axons extending to the posterior pituitary to release OT and AVP to general circulation without vasculature
Anterior pituitary
- Made of glandular tissue
- Synthesizes 6 hormones that flow through the blood to the anterior pituitary
- Stimulate or inhibit the release of other hormones
Contains Median eminence/primary plexus
- Stimulate or inhibit the release of other hormones
Median eminence/primary plexus
- Connection from axons of the hypothalamus → anterior pituitary
- Where the hypothalamus releases hormones to anterior pituitary as a private blood supply
Wolffian ducts vs Mullerian ducts
Mullerian ducts: Precursors to female internal structures
Wolffian ducts: Precursors to male internal structures
SRY gene
On Y-chromosome that causes undifferentiated gonads to develop into testes
Females do not have SRY gene so gonads develop into ovaries and Wolffian ducts degenerate
Organizing vs Activating effects
Organizing: Produce long lasting structural effects, usually younger in life, sensitive periods
Activating effects: More temporary, continuing only while the hormone is present or shortly after
Adulthood affects
Sensitive periods
Period when an animal is sensitive to organizing effects, usually pre/post natal
ex. 1st trimester where sec hormones determine the development of male or female genitals
2D: 4D ratio
- 2D: index finger, 4D: ring finger
- Ratio of lengths is different between men and women
- Women = 1
- Men = 0.98 (4D longer than 2D)
Hormone Transport and release
- Lipid soluble hormones use carrier proteins to travel through the blood whereas protein and peptide hormones are soluble in the blood
- Lipid soluble hormones not stored, protein and peptide hormones are stored in vesicles and released in response to a stimulus
- 90% of glucocorticoids are bound to a protein
Types of Hormone receptors
- Protein and peptide receptors, Steroid hormone receptors
Protein and peptide hormone receptors
3 domains
- Extracellular: binds ligand
- Transmembrane
- Cytoplasmic: enzyme activates intracellular proteins via phosphorylation
Regulated, don't last foreverSteroid hormone receptor
Intracellular and Membrane-bound receptors
Intracellular steroid receptors
- Within the cell, regulate gene expression via hormone response elements
- Long lasting, >30 min
3 Domains: C-terminal, Central, N-terminal
HRE: located on DNA where ligand/receptor complex binds to the promotor region to regulate gene expression
Membrane bound steroid receptors
In plasma membrane or mitochondria
- Regulates enzymes, fast acting
- Observed in the effects of corticosterone on newt mating behaviour
- Corticosterone decreases clasping (mating) behaviour quickly
Neurosteroids
Steroids synthesized in the brain
Etiene Baulieu
Etiene Baulieu
- Observed that rats have decreased levels of DHEA in blood and increase in the brain
- He looked at orchidectomy and adrenalectomy in rats but still saw high levels of DHEA in the brain
- Hypothesized that DHEA is made from cholesterol in the brain
