Lecture 8

Question 1

What is a hormone

Answer 1

A chemical, usually secreted by an endocrine gland, that is conveyed by the bloodstream and regulates distant target organs and tissues. These are slow, non-precise, but have more substantial effects on biology. Neurotransmission is precise. Endocrine gland: a gland that secretes hormones into the bloodstream to act on distant targets. Endocrine go into bloodstream. Exocrine go into ducts. Biphasic stress: slow hormonal response and fast neural response.

Question 2

Four types of chemical communication

Answer 2

Endocrine communication: going into bloodstream to target cell. Pheromone: odor-based communication between two members of the same species. Allomone communication: odor-based communication between members of different species. Synaptic communication - same as before.

Question 3

Major endocrine glands and their functions

Answer 3

Hypothalamus: control of hormone secretions. Pineal gland: reproductive maturation, body rhythms. Anterior pituitary: hormone secretion by thyroid, adrenal cortex, and gonads; growth. Posterior pituitary: water and salt balance. Thyroid: growth and development, metabolic rate. Pancreas: sugar metabolism. Gut: digestion and appetite control. Gonads: body development, maintenance of reproductive organs in adults.

Question 4

Major classes

Answer 4

Amine, peptide, and steroid. Peptide and amine are fast.

Question 5

Behavioral endocrinology

Answer 5

1) remove gland: finding that the central mechanism in the chicken/rooster was not in CNS but in the gland. 2) knockout - delete a gene for a given hormone. 3) Individual differences analyses via blood: not a lot of relationship between hormones and behavior. Autoradiography: inject radioactively labeled hormone, place tissue on photographic film to index which brain regions accumulated most labeled hormone. Immunocytochemistry: detects a particular protein in tissues, antibody recognizes and binds to protein, chemical methods localize proteins in tissue.

Question 6

Hypothalamus, pituitary gland, and neuroendocrine cells

Answer 6

Hypothalamus - neural region central to homeostasis that links nervous system to endocrine system. Does thermoregulation, sex, stress, reproductive cycles, hunger. Pituitary gland - central endocrine gland, serves as a bridge between hypothalamus and periphery. All hormones in the body are modulated by this system. Neuroendocrine cell: neuron that releases hormones into local or peripheral circulation. They release hormones instead of neurotransmitters, bridge between nervous system and hormonal system.

Question 7

Posterior pituitary

Answer 7

Releases oxytocin and vasopressin. The anterior pituitary drives a lot like sex and stress. Paraventricular - bind to neuroendocrine cells, posterior releases into capillaries that go into periphery.

Question 8

Oxytocin

Answer 8

Implicated in a large range of maternal, social, and affiliative bonding. Lactation and the letdown reflex and uterine contractions during childbirth. Released during orgasm. In animals, it facilitates monogamy. Fuels trust and romantic attachment (in contrast to dopamine). Intranasal oxytocin elevates empathy, generosity, bonding, and in-group affiliation. It may elevate out-group distancing.

Question 9

The regulation of hormones - a negative feedback circuit

Answer 9

Hypothalamus helps mediate the release of hormones, hormone released into bloodstream, hormone binds with hypothalamus and tells it there is enough hormone, so don’t need to release more. There are other nuclei involved in hormone regulation - hippocampus and cortisol.

Question 10

Anterior pituitary

Answer 10

Front division of pituitary gland - secretes 6 tropic hormones. Neuroendocrine cell bodies in hypothalamus produce releasing hormones. Releasing hormones traverse the hypothalamic-pituitary portal system (set of veins between hypothalamus and pituitary gland) to control pituitary’s release of tropic hormones. Cells in anterior pituitary respond to releasing hormones by releasing/inhibiting release of their own hormones, known as tropic hormones. Tropic hormones travel through the bloodstream to regulate endocrine glands throughout the body. These are second hormones released.

Question 11

Anterior pituitary order of events

Answer 11

Hypothalamus - releasing hormone (hypothalamic pituitary portal veins) - pituitary gland - tropic hormone - target endocrine gland - target hormone.

Question 12

Two anterior pituitary hormones act on gonads

Answer 12

Gonads - testes or ovaries. Gonadotropin releasing hormone (GnRH) - hypothalamic hormone controlling release of FSH and LH from pituitary. This is the first hormone released. Gonadotropins (FSH and LH) - anterior pituitary hormone stimulates cells of gonads to produce sex steroids and gametes. Oral contraceptives. In males - sex steroids are androgens (testosterone) and gametes are sperm produced in testes. Sex steroids in women are progestins (progesterone) and estrogens (estradiol) and gametes are ova (eggs) produced in ovaries. Ovarian hormones produced in cycles - menstrual cycle (28 days in humans). Birth control is piggybacking on negative feedback loop, so you’re not releasing GnRH and not initiating the ovulatory cycle.

Question 13

Neural circuits for reproduction in rodents

Answer 13

These are interesting to study when looking at sexual responsivity. Androgens act on hypothalamic medial preoptic area (mPOA) and medial amygdala in male rats. Estrogens affect neurons in ventromedial hypothalamus and periaqueductal gray (site of endogenous opiods) in female rats. Basal ganglia/ventral striatum is relevant to processing reward cues and dopamine transmission. Lordosis - female receptive posture in four-legged animals.

Question 14

Human sexuality

Answer 14

In addition to areas activated in rodents, areas activated in humans include much of the cortex including the orbitofrontal cortex (reward sensitivity), ventromedial prefrontal cortex (reward sensitivity), parietal cortex, anterior cingulate cortex, and insular cortex (somatotopographic map of the body). Amygdala and prefrontal cortex shut down during orgasm (deactivation of amygdala in both men and women, deactivation of prefrontal cortex in women). Switch from parasympathetic to sympathetic during orgasm.

Question 15

Male orgasm

Answer 15

Activation in mesolimbocortical dopamine circuit (ventral tegmental area, nucleus accumbens). Comparable to that induced by heroin. Male orgasm associated with deactivation of the amygdala.

Question 16

Female orgasm

Answer 16

In addition to activation in mesolimbocortical reward regions (VTA, nucleus accumbens), other areas go silent. Deactivation in the orbitofrontal cortex, ventromedial prefrontal cortex, and amygdala.

Question 17

Gonadal steroids and sexual behavior

Answer 17

Gonadal steriods critical to activating sexual behavior (ex castration) but do not appear to be related to individual differences in sexual behavior in either rodents or humans. No correlation between the amount of androgens and sexual vigor. Mammals overproduce androgens - ceiling effect for individual differences. After castration, rats that had previous high drive return to it despite being given the same amount of testosterone as medium and low dose rats.

Question 18

Gonadal steroids and aggressive behavior

Answer 18

In humans and rats, growing research suggests that there are individual differences in testosterone levels and aggression/dominance. Elevated testosterone is associated with elevated aggression in many species. In seasonally breeding species, intermale aggression varies with seasonal levels of changes in testosterone. Rats - testosterone and biting. Humans - testosterone and dominance (self-reported and displayed), but not aggression. Levels rise in winners and fall in losers in competitions ranging from wrestling to chess. Simply watching your sports team/political candidate modulates testosterone. Dominance sometimes leads to violence.

Question 19

Sexual differentiation

Answer 19

What drives basic biological sex (developing testes and sex differentiation) is genes, driven by SRY on Y chromosome. Deviations: congenital adrenal hyperplasia - genetically female, but there is a hypersecretion of androgens. Physically strong male appearance, 40-50% are homosexual (suggests androgens affect sexual orientation). Androgen insensitivity syndrome - XY genome, release testosterone but receptors are limited, so there’s a reduced responsivity to testosterone. Failure to develop male sex organs, some cases where they look female but don’t get period, go to the doctor and find out they are genetically male.

Question 20

Gonadal hormones direct sexual differentiation

Answer 20

Organizational effect - androgen (testosterone) exposure during early development is central to sexual differentiation of both genitalia and brain. Androgens have organizational effect only during specific sensitive periods (early development, adolescence). Rat study - untreated males and females display normal behavior (mounting and lordosis). Females treated with testosterone will mount. Castrated males perform lordosis. They were treated with testosterone or castrated respectively (and then males treated with estradiol later on).

Question 21

Sexual dimorphism in rodents

Answer 21

Pretty clear difference in rats in some regions, less so in humans. Males have larger volume in nucleus within hypothalamic preoptic area (POA). Dubbed sexually dimporphic nucleus of POA (SDN-POA). Male rodents castrated at birth had smaller SDN-POA as adults while females androgenized at birth had larger SDN-POAs as adults. As a whole, testicular androgens during sensitive periods have sustained effects on the brain (not just peripheral effects on the body).

Question 22

Sexual dimorphism in humans

Answer 22

Some studies identify differences in neural structure and function between males and females. Extensive overlap between gray and white matter in both. This challenges the notion of categorical distinctions between male and female brains, highlights a “mosaic male and femaleness continuum.” MRI does not have the spatial resolution to detect structural differences in sub-nuclei and/or receptor affinity.

Question 23

Sexual orientation in non-human mammals

Answer 23

Homosexual behavior seen in other species - mountain goats, swans, dolphins, etc. More common among apes and monkeys than prosimian primates like lemurs (suggests greater brain complexity makes homosexual behavior more likely, within apes - more common in apes that have more prefrontal development). Reliable differences in preoptic area (POA) in gay vs straight rams that are secondary to testosterone exposure during fetal development.

Question 24

Sexual orientation in humans

Answer 24

Study of interstitial nuclei of the anterior hypothalamus (examined post-mortem). INAH-3 is larger in men and larger in straight men as opposed to gay men. This is cross-sectional so can’t look at genes vs experience (can’t say the variation in androgen exposure is genetic). Gay males look more similar to females than straight males, suggests some biological foundation to homosexuality. Ex: effects of anosmia on maternal grooming of male pups and the development of sexual dimorphism in the rodent brain (they don’t smell the sex of the offspring - pheromone in urine, treats offspring the same, failure to get sexual dimorphism in rats that didn’t get prototypical grooming postnatally - early postnatal environment has important effect on establishing sexual dimorphism in the brain). Ex: effect of maternal grooming on female rat pup estrogen and oxytocin sensitivity and future maternal attentiveness (amount of estrogen released during grooming affects maternal attentiveness when she herself becomes the mom).

Question 25

Human sexual orientation continued

Answer 25

Evidence that lesbians are exposed to slightly more fetal androgens (finger length). Girls with congenital adrenal hyperplasia more likely to report a homosexual orientation. Sexual orientation is partly heritable (50%). Sexual preferences are there from the beginning - any social influence would have to be acting very early in life without conscious awareness. No reliable method to change sexual orientation. Current perspective is that we do not choose our sexual orientation - combination of genetic variation, exposure to androgens pre-natally and post-natally.

Question 26

Stress and the HPA axis

Answer 26

Immediate stress response mediated by the noradrenergic system involving activation of CNS neural activity and sympathetic nervous system via norepinephrine (initial response like hands sweating). Subsequent stress response is hormonal involving secretion of stress hormone cortisol via the HPA axis - central to stress physiology. CRH - corticotropic releasing hormone. ACTH - adrenocorticotropic hormone. Secretion of cortisol has similar effects to activation of sympathetic nervous system (pupil dilation, elevated heart rate, immune system suppression). Prepares body for action - release of cortisol from adrenal glands. Shuts down immune system, digestion, other things that aren’t critical to survival. Drives metabolic resources to the muscles that can facilitate movement. Takes 20-30 mins for cortisol to start operating, steroid receptors are internal to cell, so cortisol has to go through cell. Process is essentially threat stimuli - activates amygdala - amygdala sends output to hypothalamus - hypothalamus releases CRH - CRH goes to anterior pituitary gland - anterior pituitary releases ACTH (a tropic hormone) - ACTH passes through bloodstream to adrenal glands - adrenal glands release cortisol into the blood.

Question 27

Cortisol, stress, and depression

Answer 27

Cortisol is hugely adaptive in short-term usage, but prefrontal cortex allows us to be stressed for a much longer time, and these stressors activate the stress response in the same way as if we saw a spider (stress is bad). We live in a stressful environment. Highly neurotic individuals are good at activating the stress response for things it was never meant for. Chronic cortisol associated with - hippocampal atrophy (one major cortisol receptor area), over time downregulates receptors, and you see cell death. This is the reason depressed people have worse memory. Inflammation - risk for illness and diabetes. Neuroticism and depression - people who are depressed have more intense cortical response over the course of the day in response to stressors. Dexamethasone - antagonist designed to shut stress hormone down - suppression test: if you’re depressed, brain will override this and be stressed despite being given this thing that’s supposed to make you not stressed.