PSYC 304 Exam 4

peptide hormones

chemical signalling molecules composed of 10-100 amino acids

• water-soluble

• effect endocrine system

• found only on the cell surface

• ex. insulin and glucagon

amine hormones

single amino acid signalling molecules

• water or fat-soluble

• found on cell surface or intracellular

• ex. epinephrine and norepinephrine

amino acid functions

• alters protein synthesis

• alters metabolism of cells

• alters neural activity (affecting ion channels)

• act quickly (second - minute timescale

steroid hormones

derived from cholesterol, fat soluble

• can go inside the cells and bind to DNA

• Increase gene transcription/protein synthesis

• results take longer to show and are more long-lasting

• changes the architecture of cells

• different proteins can be generated from one steroid hormone due to receptor co-factor

types of hormones

• corticosteroids

• sex steroids (androgens and estrogens)

gonadal/sex hormones

most common androgen = testosterone

• dihydrotestosterone (DHT)

most common estrogen = estradiol

sex hormone cycle in the body

increased release triggered by hypothalamus → anterior pituitary releases them → gonads: male testes release testosterone and female ovaries release estradiol

where do sex hormones come from?

released by sex glands

• ovaries: release more estrogens than androgens

• testes: release more androgens than estrogens

• regulated by negative feedback mechanisms

adrenal cortex also releases small amounts of sex hormones

sexual determination in utero

two types of chromosome combinations: XX (female), XY (male)

• sex is not as simple as the chromosomes

gonadal sexual development in utero

undifferentiated until 6 weeks of development - after, if an SRY gene is present, the Y chromosome begins testes development

• if SRY gene is not present, gonads will develop as female

• gonads made of medulla (inside) and cortex (outside) - cortex forms ovaries and medulla forms testes

gonadal ducts

Wolffian = male: develops into epididymis, vas deferens seminal vesicles

Mullerian = female: develops into fallopian tubes, uterus, inner vagina

female (XX) sexual development

• no Y chromosome = no testosterone

• Wolffian ducts shrink away and Mullerian ducts grow due to no T (around week 7)

male (XY) sexual development

• SRY gene = SRY protein = Y chromosome

• testes produce testosterone and anti-mullerian hormone (AMH) - causes Mullerian ducts to shrink and T causes Wolffian ducts to grow

• T masculinizes other structures (aided by DHT, which is converted from T by 5 alpha-reductase) - prostate gland, scrotum, penis

what controls if a fetus develops into a male or female?

presence or absence of testosterone

• not by estrogen

• sex chromosome = sex of the gonad

• gonadal hormones = sex of rest of body

androgen insensitivity syndrome

genetic defect that causes no presence of functional androgen receptors

• no effect of T during development despite XY chromosomes - testes form but remain internalized

• AMH causes mullerian ducts to shrink, but Wolffian ducts do not develop

• Female external genitals develop and estrogen present causes female secondary sex characteristics

• look and behave like an XX woman, but no menstruation or body hair

androgenital syndrome

caused by congenital adrenal hyperplasia which results in fetuses not producing enough cortisol = higher than normal levels of T (cortisol blocks androgen receptors)

• T masculinizes XX fetus

• Primordial gonads still form ovaries, Wolffian and Mullerian ducts grown, external genitalia are intersex

• Many act/look like males at puberty

Turner’s syndrome

only have one sex chromosome - a single X

• person has recognizable ovaries, but they are underdeveloped

Non-functioning 5𝝰-reductase

T cannot be converted to DHT

• XY fetus will develop testes/male internal reproductive structures, but external genitalia will not masculinize fully

• Androgen production increases at puberty and a penis (smaller than normal) will develop

rat sexual behaviour

starts with a female (ovulate every 4-5 days)

• Step 1: female displays proceptive behaviours (darting, hopping, ear wiggling) during ovulation

• Step 2: male begins to mount receptive female

• Step 3: female arches back and moves tail to one side (lordosis)

• Step 4: male then intromits (inserts penis) and thrusts

• Step 5: repeat steps 2-4 until ejaculation

rat sexually stereotyped behaviours

females: lordosis, darting, hopping, ear wiggling

males: mounting, intromissions

• primary measures of whether sexual brain has developed more male or female-like

how do sex hormones regulate sexual behaviour

organizational effects

activational effects

organizational effects

permanent/non-reversible changes in body/brain occurring during development

• hormones exert these effects during critical periods of development - in utero and puberty

activational effects

on body/brain - behaviour after development

• typically after sexual maturity (puberty)

• transient effect, varies with amount of hormones in bloodstream

neural sexual development in rats

development of parts of brain responsible for sexual behaviour continues to occur after birth - regulated by presence/absence of T

• can do hormone studies on rats because their brains are still developing

altering male rat sexual behaviour

castrating males in 1st week after birth = de-masculinizes and feminizes behaviour in adulthood (not observed if rats are castrated after initial critical period)

• replacement T in adulthood doesn’t reinstate male-like behaviours (past critical period)

• giving estrogens to adult male rats castrated neonatally can induce female behaviours

altering sexual behaviour in female rats

give T to female rat ~ 1st week after birth = defeminizes and masculinizes sexual behaviour in adulthood - not observed if given after puberty

• T given to these females in adulthood induces male sexual behaviours

• giving more estrogen to a neonatal female can also cause male behaviours

aromatization hypothesis

aromatase enzymes convert T to estradiol in the brain

• early exposure to estradiol is what masculinizes the rat brain

why doesn’t estrogen in the brain masculinize female fetuses?

𝝰-Fetoprotein is in blood of male and female neonates

• binds to free floating estradiol and prevents its entry into the brain

• it does not bind to androgens - T can enter brain and be converted to estradiol

• when too much estrogen is injected into female rats, the bloodstream is flooded with estrogen and ends up in the brain

evidence for aromatization hypothesis

1. neonatal estradiol masculines behaviour - in males, this saturates all 𝝰-fetoprotein molecules in bloodstream, extra estradiol can pass into brain

2. Aromatase is present in neonates

3. Blocking aromatase/estrogen receptors disrupts masculinizing effects of T

4. Female 𝝰-fetoprotein knockout mice show more male/less female like behaviour

5. DHT cannot be converted to estradiol, has no masculinizing effects when given early in development in rats

neural sexual development in primates

Sex hormone binding globulin (SHBG) protects fetal primate brain from estrogens

• can bind to androgens and estrogens

• 𝝰-fetoprotein is not responsible

• early treatment with either estrogens or androgens in pregnant primates can masculinize behaviour of female offspring (unlike rats)

• some synthetic estrogens that are not blocked can also masculinize primate brain

changes in brain during sexual development

preoptic area of hypothalamus

spinal nucleus of bulbocavernosus in spinal cord

sex differences with the preoptic area of hypothalamus

• this are specifically important for sexual behaviour

• nucleus is larger in males than females

• T injections in females = bigger nucleus

• castration in males = smaller nucleus

• agrees with aromatization hypothesis

sex differences with the spinal nucleus of bulvocavernosus (SNB)

rats have more motor neurons in the area because they need more muscles for the penis

• muscles in females die out early

• androgen injection in females spares some SNB motor neurons

• castration in males causes them to die too

• contains androgen receptors

• retained in human females until adulthood because it helps constrict vaginal opening

sexual orientation vs. sexual development

they are different - developmental basis of both not well understood

sexual orientation

determined early in development, due to biological factors

• males: 52% of monozygotic, 22% of dizygotic twins both homosexual

• females: 46% monozygotic, 16% dizygotic twins both homosexual

prevalence of homosexuality

2-10% of pop in Western countries

hormones and sexual orientation

homo- and heterosexuals do not differ in hormone levles

• in animals, castration or perinatal T can cause same sex preference in many species

• the more older brothers a boy has, the more likely he is to be gay - maternal immune response to neutralize Y proteins in the body

neural differences and sexual orientation

some structural differences potentially

• anterior hypothalamus differences

• differences in regions related to body perception

• lesbians tend to show markers indicative of fetal androgen exposure (longer ring fingers)

activational effects of hormones in male sex behaviour

removing T effects reduces sex drive (need some T to have it) - replacement T will bring it back to normal levels

• for castrated males too

• relative sex drive and T levels are uncorrelated - T injections do not increase sex drive, they just have to have some androgen to have it

• takes a while to set in - cells becoming receptive to T

• other factors appear to control sex drive

neural regulation of male sex behaviour

sufficient levels of T in bloodstream primes certain brain region to be receptive to sexual stimuli - specifically mPOA and medial amygdala

• does not cause sexual behaviour but is important for it

• activational effect

• copulatory behaviour to ventral midbrain → projects to basal ganglia for mounting behaviours → spinal cord (stimulates erections)

evidence for T/Estradiol regulation of male sexual behaviour

• mPOA/medial amygdala lesions disrupt sexual beahviour

• mPOA stimulation initiates sexual behaviour

• in castrated males - administration of T or estradiol into just the mPOA reinstates sexual behaviour

hormone regulation of female sex behaviour

in rats, estradiol increases ~2 days before ovulation (causes brain to make progesterone receptors) (cycle length = ~4-5 days)

• when progesterone and estrogen peak, ovulation occurs (fertility and sexually stereotyped behaviours)

• estrogen peaks → then progesterone peaks

neural regulation of female sex behaviours

ventromedial hypothalamus (VMH) monitors changes in hormonal values, constantly detecting hormone levels in blood

• estradiol causes VMH and periaqueductal gray to have modifying ability, produce proteins necessary for lordosis

hormones hitting their peaks activates multisynaptic pathways that include motor areas

signals output through spinal cord → lordosis

evidence for estradiol regulation of female sexual behaviour

1. VMH/PAG lesions disrupt lordosis

2. Implantation of estrogens into VMH reinstates lordosis in ovarectomized females

hormonal pathway for sexual behaviour in female rats

1. sexual signals: pheromones/odours

2. olfactory circuits reach the hypothalamus, hormones induce estrus

3. tactile stimuli from male

4. lordosis is activated

5. presentation of the vagina

6. sex begins

hormones and human female sexual behaviour

• estrogen: sexual motivation/behaviour is not as tightly linked to estrogens released during menstrual cycle - ovariectomy does not have reliable effects on them (important for ovulation)

• androgens: T levels can correlate with measures of sexual motivation - following ovariectomy, replacement T rekindles sexual motivation

menstrual cycle and female sexual behaviour

behaviour patterns change during cycle - greater probability of having intercourse/achieving orgasm as ovulation approaches

• women appear to be more attracted to stranger’s smell than their partner’s during ovulation

4 major stages of reproductive behaviour

1. sexual attraction

2. appetitive behaviour

3. copulation

4. post-copulatory behaviour

sexual attraction stage

• traits that are the products of sexual selection pressures

• pair-bonds (stay together after copulation) or sexual-bonds (separate after copulation)

• men seem to overestimate women’s interest

appetitive behaviour stage

• if mutually attracted, display species-specific behaviour that establish, maintain, promote sexual interaction

• females display initial proceptive behaviours (approaching males, staying close to them)

copulation stage

• if both animals display appetitive behaviours

• involves one or more intromissions into females

• depends on female’s sexually receptive behaviour/in heat

• all mammals employ internal fertilization (fusion of gametes = zygote)

post-copulatory behaviour stage

• will not mate again until refractory period has elapsed (can be minute to months long)

• many mammals will mate sooner if provided a new partner (Coolidge effect)

• some animals will be in copulatory lock where their penis swells so much that they cannot remove it from the female

pheromones

chemical signals that communicate info between animals to help coordinate reproductive activities

• special structures in animals: vomeronasal organ (VNO), accessory olfactory bulb

pheromone structural path

VNO specialized receptor cells near olfactory epithelium → accessory olfactory bulb → medial amygdala → mPOA (integrates hormonal and sensory info and coordinates motor patterns of copulation)

male sexual response patterns

always have an absolute refractory period after orgasm - often followed by renewed arousal

• activity seen in subcortical areas, penile stimulation activates right insula and secondary somatosensory cortex

female sexual response patterns

show a lot more variation than men - absolute refractory after orgasm and no renewed arousal, renewed arousal, never reach orgasm, etc.

• clitoral stimulation and orgasm associated with hypothalamus, amygdala, cerebellum, cingulate, brain stem, basal forebrain

why do we have to eat?

to maintain energy levels of the body

how does the body use energy?

1. basal metabolism: ~60% of energy usage maintains body heat and other resting functions (life-sustaining functions) (varies with body weight)

2. active behavioural processes: ~25% is for behaviours other than rest (vary depending on activity level)

3. digestion of food: ~15% is to process food, break it down into molecules (varies with type of food)

4. remainder gets stored as energy reserves

rate of basal metabolism

kilocalories/day = 70 x weight^0.75

basic nutrients

• carbohydrates

• amino acids

• lipids (fats)

• vitamins and minerals

carbohydrates

~4 kcal per gram, glucose is primary fuel of body, all other carbs get converted to glucose

• short-term storable form is glycogen: stored in liver and muscles

amino acids

~4 kcal per gram - comes from proteins, basic building blocks for all cells

• 20 types, 9 cannot be produced by the human body (essential amino acids)

• can be converted to glucose

lipids

~9 kcal per gram - long term energy source

• can be converted to free fatty acids as an alt energy source for most cells of the body

• can be stored long-term

• use when blood sugar is low or under food deprivation as ketones

vitamins and minerals

needed to assist in bodily functions (digestion, cell building, homeostasis)

steps of digestion

1. chewing (mastication)

2. saliva (lubrication)

3. swallowing (getting there)

4. stomach - storage and breakdown (HCl, Pepsin)

5. duodenum - absorption

6. gall bladder and pancreas fluids further break down food in duodenum (proteins → amino acids/starch → simple sugars)

7. bile from liver (stored in gall bladder) breaks down fats

8. remaining water and electrolytes absorbed by large intestine or ejected via the anus

   whole process takes 18-24 hours

glucose regulation

done by the pancreas

• two main hormones: glucagon (converts glycogen into glucose - increases blood sugar) and insulin (decreases blood sugar)

• negative feedback system

primary actions of insulin

1. promotes use of glucose as primary energy source: most cells need insulin to get glucose in cells, brain is one exception (used glucose without need for insulin)

2. converts bloodborne fuels to storable forms: glucose → glycogen (muscles/liver), glucose and fatty acids → adipose tissue (body fat), amino acids → protein (muscles)

mechanisms controlling insulin release

• brain (via vagus nerve): sight/smell/taste/thought of food can trigger insulin release before food hits gut (cephalic phase)

• other hormones in bloodstream released by gut during digestive phase

• nutrients/glucose entering bloodstream, signal pancreas to release insulin (absorptive phase)

glucose detection by the brain

glucodetectors in liver → vagus nerve → nucleus of solitary tract (NST) → hypothalamus (informs brain of glucose levels and contributes to hunger)

diabetes mellitus (Type 1 [juvenile-onset] diabetes)

• pancreas stops producing insulin, excess glucose in blood stream

• brain cannot use all of it, and cells of body cannot use glucose without insulin, start using fatty acids

• when left untreated, diabetes can lead to more eating that doesn’t satisfy hunger and paradoxical weight loss (brain thinks we are starving because we are not getting any glucose in the cells)

• Type II diabetes = sensitivity to insulin (adult onset)

is insulin a satiety signal?

if you lower an animal’s insulin level, it becomes hungry and eats a large meal

• but, give it a large amount of insulin - converts most glucose to fat, less glucose in bloodstream

• brain detects glucose deficit, initiates hunger - animals will eat a large meal again

is glucose a satiety signal?

not entirely - untreated diabetes leaves a lot of glucose in bloodstream, but still hunger

• glucose levels can stay relatively stable for days, but we still get hungry

multiple signals in addition to insulin and glucose contribute to hunger and satiety

why do we get hungry: set-point theory

idea that the body has a predetermined weight range that it aims to maintain

• hunger as an energy deficit - negative feedback system maintaining homeostasis

• two types: glucostatic and lipostatic

glucostatic set point theory

eating is controlled by deviations from a hypothetical blood glucose set-point - focused on blood sugar levels dropping or rising

lipostatic set point theory

eating is controlled by deviations from a hypothetical body fat set point

problems with set-point theories

• evolution argues against it: food availability was once inconsistent, so it was better to eat large quantities and store calories

• fails when tested: drinking high glucose/caloric drinks before meals doesn’t reduce eating significantly

• ignores other factors that stimulate eating: different tastes of food (dessert after dinner), social factors increasing eating

positive-incentive theory

anticipated pleasure of eating is the main factor controlling feeding

• evolved to crave food not because of a deficit, but because we like it

factors that determine what we eat

• taste preferences/aversions: some tastes have high incentive values (sweet, salty, fatty = more glucose), others are learned from experience (like bitterness) (can condition taste aversion)

• learning to eat vitamins and minerals: can learn to select what you are lacking in - rats will choose the high B1 food when they are low in it out of 10 different foods

factors that influence when we eat

pavlovian conditioning: environment cues associated with eating can elicit hunger/feeding

• caused by expectation of food

• pair food with a tone, rats will always eat when they hear the tone, even if they just ate

pre-meal hunger: time of day one usually eats at can trigger hunger - conditions brain/body to prepare for incoming food, stomach growls to prepare for food

pre-meal hunger and changes in blood glucose

study found that when rats were provided with unlimited food, their glucose levels remained constant throughout the day except before meals were initiated - 10% drop in glucose

• glucose not directly responsible for feeding - if food is removed, glucose levels return to previous homeostatic levels within 10-15 mins (like if the meal was consumed)

• decline related to intention to eat - drop is preceded by increased insulin in anticipation for eating

factors that influence satiety

• social influences: humans and animals eat more in groups vs. alone (take bites together, eat similar amounts of food)

• sensory specific satiety: humans and animals eat more calories if they are given varied diet

  • new taste = more consumption

physiology of hunger and satiety

• liver: signals brain about what’s in the bloodstream via vagus nerve - receives blood from small intestine and has detectors for glucose and fatty acids (everything you eat will first pass through the liver)

• decides if food is right to go into general circulation

  • can trick liver into thinking glucose/fat levels are low (2-DG = competes with glucose for absorption, methyl palmoxirate = disrupts metabolism of fatty acids) - causes increase in feeding, takes nutrients from intestines instead

• cutting vagus nerve abolishes effect of drug injection

satiety/hunger signals

use multiple hormones to signal brain to start/stop eating

• signals can suppress hunger before food is fully digested

• arcuate nucleus of hypothalamus (ANH) contains appetite controllers governed by circulating levels of hormones

• only way gut can communicate with brain is through hormones in blood

hunger signals from stomach

CCK, bombesin, somatostatin

• peptide Ghrelin levels remain high during fasting and drop during meal - acts on NPY cells in ANH

hunger signals from liver

detects changes in blood glucose, direct input to brain via vagus nerve

hunger signals from pancreas

insulin

hunger signals from intestines

PYY and GLP-1 (decrease appetite and rewarding aspects of food, oppose ghrelin)

• fast-acting - PYY acts on NPY cells in ANH, GLP-1 acts on POMC cells in ANH

hunger signals from fat cells

leptin, gives continuous feedback on body’s energy stores (removal of fat gets rid of this satiety signal and increases hunger)

• defects in production can lead to overeating

arcuate nucleus of hypothalamus appetite system

first-pass appetite control center

• 5 main hunger hormones: insulin (pancreas), leptin (fat cells), GLP1/PYY (intestines), ghrelin (stomach)

relies on two sets of proteins: POMC and CART neurons (inhibit appetite and increase metabolism), NPY and AgRP neurons (produce neuropeptide Y, stimulate appetite and inhibit POMC neurons, AgRP competes with 𝝰-MSH for receptors)

neural basis of hunger and satiety

ventromedial hypothalamus: lesions to the nucleus cause animals to become obese, starts with massive consumption that achieves new weight → then maintenance of that weight

• do stop eating eventually - become finicky eaters (give lesioned rats less palatable foods, they will show minimal weight gain)

• VMH not the satiety centre - instead it regulates energy metabolism

• VMH lesions increase insulin levels - decreases breakdown of body fat into usable forms

Lateral hypothalamus: lesion caused rats to stop eating - force feeding rats will get them to start eating again

• causes problems with the actions of eating, not hunger

many regions including other hypothalamic subregions, amygdala, frontal cortex are also involved in hunger and satiety

VMH lesions

destroy axons projecting from paraventricular nuclei of the hypothalamus - lesions of the fibres along produces hyperphagia and obesity

arcuate neural circuitry and appetite - long term appetite control

activate POMC/CART neurons and inhibit AgRP/NPY neurons

• POMC/CARRT neurons inhibit lateral hypothalamus (LH) using 𝝰-melanocyte stimulating hormone

arcuate neural circuitry and appetite - short term appetite increase

inhibits PVN cells using NPY - release AgRP in LH and block 𝝰-melanocyte stimulating hormone, leading to increased LH activity

• ghrelin released by stomach when empty stimulates AgRP and NPY

arcuate neural circuitry and appetite - short term appetite decrease

PYY inhibits AgRP/NPY neurons, which disinhibits (increases) PVN activity

GLP 1 stimulates POMC/CART neurons, which inhibits LH activity

• PYY/GLP-1 released from intestines in response to a meal

bypassing the hypothalamic feeding circuit

prefrontal cortex and amygdala also can recognize feeding cues - leisions to these areas, disconnection of amygdala-LH path abolishes conditioned increases in feeding (only disrupt cue-induced feeding

neurochemistry of hunger and satiety

serotonin - major satiety signal

• 5-HT treatment can decrease feeding and amount of food consumed per meal, but not number of meals per day

• also shift food preference away from fatty foods - acts as a short term satiety signals associated with meal consumption

• inhibits release of NPY in the PVN of hypothalamus - disinhibits PVN neurons to promote satiety

anorexia nervosa

obsession with body weight/image and food - ~1% of population (mostly women)

• self-induced starvation leading to significant low body weight in context of age, sex

• often presents with BMI of <15 kg/m2

• fear of gaining weight

• distorted view of body - lack of recognition of seriousness of weight

• obsessed with food, show higher than normal insulin release to food anticipation, often disgusted with sweet/fatty foods

anorexia treatments

very few effective ones

• less than 30% show long term recovery

• ~10% die of starvation/suicide

anorexia causes

• psychological: positive-incentive value for food goes up during starvation, meals are a disruptive event on the body, can cause conditioned taste aversions to food

• biological: info processed in certain brain regions altered

  • abnormal frontal activation patterns

  • abnormal increases in amygdala activity to palatable tastes

  • feeding hormone levels reduced (AgRP, NPY, leptin)

  • 5-HT abnormalities

obesity

excessive adipose tissue

• adult males = >25% and females = >30% fat content

• obesity = BMI > 30