Pinel Lecture Notes - Chapter 1 | Pinel Chapter 2 | Pinel Chapter 3 | Pinel Chapter 4 -- Neural Conduction and Synaptic Transmission | Pinel Chapter 5 -- Research Method in Biopsychology | Pinel Chapter 6 -- Human Brain Damage & Animal Models | Pinel Chapter 9 NS Development | Pinel Chapter 10a -- Eating | Pinel Chapter 11 -- Hormones & Sex | Pinel Chapter 12 -- Sleep | Chapter 13 -- Drug Action and Addiction | Chapter 15 -- Neuroplacticity | Biopsychology of Stress and Illness
RESEARCH PROBLEMS AND HYPOTHESES
& Operational Defininitions
A. Identifying a Research Problem
A problem is an unanswered question.
The problem selected for study depends in part upon the researcher's
Interests,
Skills,
Inventiveness,
Creativity,
Resources available
Sources determining research problems:
1. Observation of life events and asking how and/or why they do.
2. Brainstorming happens when two or more people generate ideas for research
3. Theoretical Predictions - regarding what will emerge if a particular explanatory system (paradigm) is valid.
4. Developments in Technology make possible two types of study:
1) studies to investigate old problems in new ways, usually by increases in resolution.
2) advances generate new problems. E.g. Computers leading to studies in artificial intelligence.
a. Computer Data Analysis now permits efficient accumulation, management, and analysis of huge amounts of information not previously possible.
b. Computer Control permits the precise application of stimuli, instructions, and apparatus control. In addition to recording, storing, and analyzing data.
c. Computer Simulations can be utilized to model psychological and other processes.
Knowledge of Research Literature
Science is based upon the research literature. Without it all would have to start from zero. Familiarity with the literature in a discipline can help clarify and select problems and defines what it means to be a professional.
Problems can be generated by:
a. Identifying gaps (laguna) in existing knowledge. We know about “A”, and we know about “C”. What about “B”?.
b. Encountering contradictory findings. E.g. research on extra sensory perception
c. Replication of previously published research result. “Do you believe everything you read?”
Searching the Research Literature
Psychological Abstracts
PsycINFO
World Wide Web - the NIH's National Library of Medicine is clearly the best resource for searching topics in the health sciences, including Psychology.
www.nlm.nih.gov - go to PubMed page
B. Hypotheses - A hypothesis is a statement, which if true, solves the problem. It is a tentative explanation which formulates the problem so it can be studied systematically.
1. Research Hypotheses specify a possible relationship between different aspects of the problem, i.e. between the IV and the DV.
2. Research Hypotheses are assessed by two criteria:
a. Does the hypothesis state a relationship between the variables? It should also serve to narrow the problem down to specific variables and/or contexts.
b. Is the hypothesis testable? Careful wording is important, and the terms should be definable (operationally), observable, and measureable.
C. Null Hypotheses - (not to be confused with research hypotheses)
A null hypothesis is a special type of hypothesis associated with statistical analysis.
Traditionally, a null hypothesis states for the problem at hand,
“No relationship exists between the variables”.
It is the common wisdom that is assumed (by experts or the population at large) to be true, and which the experimenter sets out to attack and prove wrong.
It is what would be expected, either by logic or by experience (prejudice?).
E.g. “A fair coin tossed 100 times, will show an equal number of heads and tails.”
Lecture 11a THE NEUROENDOCRINE SYSTEM AND THE EFFECTS OF
GONADAL HORMONES ON EARLY SEXUAL DIFFERENTIATION
Outline
1. The Neuroendocrine System
a. Pituitary Gland
b. Gonadal Hormones
c. Control of the Pituitary by the Hypothalamus
2. Early Sexual Differentiation
a. The "Mamawawa"
b. Gonads
c. Internal Reproductive Ducts
d. External Reproductive Organs
e. Brain Development
f. Conclusion
1. The Neuroendocrine System
- before I describe how hormones influence sexual development, I am going to introduce the fundamentals of neuroendocrine function, with an emphasis on the gonadal hormones
a. Pituitary Gland (use Digital Image CH11F02.BMP)
the pituitary gland is often referred to as the "master gland" because it releases a variety of hormones, called tropic hormones, which travel through the blood to other glands and stimulate them to release hormones which have diverse, long-lasting effects
the pituitary is in fact two glands: the anterior pituitary and the posterior pituitary, which dangle together from the pituitary stalk, which is attached to the hypothalamus
- strictly speaking, it is the anterior pituitary that is the master gland;
only it releases tropic hormones
b. Gonadal Hormones
- within the context of sexual behavior, the gonads (testes and the ovaries) are the
most relevant targets of the anterior pituitary, and gonadotropic hormones are its most
relevant hormones
- it is important to realize that both the ovaries and testes release exactly the same
hormones, although they release them in different amounts during various stages of
development
- the three major categories of gonadal hormones are: estrogens (e.g., estradiol),
androgens (e.g., testosterone), and progestins (e.g., progesterone); the adrenal cortex
releases the same hormones but in smaller amounts
c. Control of the Pituitary by the Hypothalamus
- a major difference between men and women is that gonadotropin release from the
anterior pituitary cycles approximately every 28 days in women, but its release varies
little from day to day in men; the release pattern for both sexes is pulsatile; attempts to
understand this male-female difference led to an important discovery
- first, it was assumed that male and female pituitaries are fundamentally different
(steady vs. cyclic), but female pituitaries implanted in males became "steady pituitaries",
and male pituitaries implanted in females became "cyclic pituitaries"; this suggested that
the pattern of anterior pituitary release was being controlled by another organ; it
suggested that "the master gland had its own master"
- attention naturally turned to the hypothalamus, the neural structure to which the
pituitary is connected; it was soon discovered that the hypothalamus controls the
pituitary in two different ways:
one way for the posterior pituitary and one for the anterior pituitary
(use Digital Image CH11F04.BMP)
- axons of neurons in the paraventricular and supraoptic nuclei of the hypothalamus terminate in the posterior pituitary (use Digital Image CH11F03.BMP)
- vasopressin and oxytocin are synthesized in the cell bodies of these neurons,
they are transported down their axons, and they are released from the posterior
pituitary into general circulation;
vasopressin facilitates reabsorption of water by the kidneys;
oxytocin stimulates contractions of the uterus and ejection of milk in women
(in orgasm, it is released in both females and males but its function in males is unknown)
- the release of tropic hormones from the anterior pituitary is controlled by other
hormones called releasing hormones;
releasing hormones are released by the hypothalamus into the ypothalamopituitary portal system, which carries them to the anterior pituitary;
gonadotropin-releasing hormone stimulates release of the anterior pituitary's two
gonadotropins:
follicle stimulating hormone and luteinizing hormone
- in general, release of gonadal hormones is influenced by feedback; usually negative, which maintains steady hormone levels;
the hormone surges observed during puberty and in females just prior to ovulation seem to be associated with switches from a negative feedback mode to a positive feedback mode (use Digital Image CH11F05.BMP)
2. Early Sexual Differentiation
a. The "Mamawawa"
- This is the MEN-ARE-MEN-and-WOMEN ARE WOMEN assumption;
the tendency to assume that men and women are distinct opposites with respect to hormones,
that men have male hormones that give them male bodies and brains and make them do male things, and
that women have female hormones that give them female bodies and brains and make them do the opposite, i.e., female things
- you will learn that virtually nothing about this fabled assumption is correct
b. Gonads
- the differentiation of male and female gonads occurs about 6 weeks after
fertilization;
at this time males and females have identical primordial gonads, each with
two parts:
a medulla and a cortex
- in males (XY), the Y sex chromosome triggers the manufacture of a protein called H-Y antigen, which causes the medulla (core) of the primordial gonads to develop into testes
- if no H-Y antigen is present (as in normal genetic females), the cortex of the primordial gonads naturally develops into ovaries
- accordingly, genetic female fetuses injected with H-Y antigen develop testes, and
genetic male fetuses injected with a drug that blocks H-Y antigen develop ovaries
c. Internal Reproductive Ducts
- 6 weeks after fertilization each fetus has two sets of undeveloped internal
reproductive ducts, one male and one female;
the undeveloped male system is called the Wolffian system;
the undeveloped female system is called the Müllerian System
- in normal genetic males, the testes release androgens in the third month and this
causes the Wolffian system to develop;
the testes also release Müllerian-inhibiting substance, which causes the Müllerian system to degenerate and the testes to descend into the scrotum;
all fetuses exposed to androgen in the third month, whether genetic male or female,
develop male ducts
- any fetus, not exposed to androgens in the third month after conception (e.g., a
normal genetic female, an ovariectomized genetic female, or an orchidectomized genetic
male) will develop female reproductive ducts
- ovariectomy refers specifically to removal of the ovaries;
orchidectomy refers specifically to removal of the testes;
castration and gonadectomy refer generally to removal of gonads
d. External Reproductive Organs
- every normal human fetus begins with the precursors of both testes and ovaries and
the precursors of both male and female internal reproductive ducts,
but female and male fetuses have the same bipotential precursor of external
reproductive organs
- the surge of androgen release in the third month of fetal development causes
this bipotential precursor to develop into male external genitals;
in the absence of androgen bipotential precursor develops into female external genitals
e. Brain Development
- there is growing evidence of differences between men and women in terms of
overall brain size, the size of specific structures in the brain, and in patterns of brain
activity
- similar to the differentiation of other body organs, sexual differences in the brain
appear to depend on exposure to high levels of androgens at developmentally crucial
times
- rats are a convenient species for the study of the sexual differentiation of the brain
because when they are born, the period during which the development of their
reproductive organs can be influenced by hormones has passed but the period during
which the development of the brain is maximally influenced by hormones is just
beginning
- most research on brain differentiation has focused on the differentiation of the
hypothalamus-controlled pattern of gonadotropin release into the steady male pattern or
the female cyclic pattern
- consistent with what you have already learned about reproductive-system
development:
rats exposed to androgens in the perinatal period (e.g., intact genetic male
rats; intact genetic female rats injected with androgen; ovariectomized female rats
injected with androgen) develop the steady, male pattern of gonadotropin release
- in contrast, rats not exposed to androgen in the perinatal period (e.g., intact genetic
female rats; ovariectomized genetic female rats; orchidectomized genetic male rats)
develop the cyclic, female pattern of gonadotropin release
- evidence supports the idea that in order to masculinize the rat brain
testosterone must be converted to estradiol--a process called aromatization
- the aromatization hypothesis is that testosterone released during the perinatal
period enters the brain and is aromatized to estradiol and that it is actually estradiol
that masculinizes the brain
[WHAT??? Are you AWAKE? Estradiol is a female hormone.]
- Sorry, there are four lines of evidence that support this theory:
(1) the enzyme necessary for aromatization is present in the neonatal rat,
(2) neonatal injections of estradiol masculinize the rat brain,
(3) dihydrotestosterone, a nonaromatizable androgen, does not masculinize the rat brain, and
(4) agents that block aromatization block the masculinizing effects of neonatal testosterone injections
- several documented differences between men and women have been seen in the
brains of humans;
men's brains are about 15% larger, have a higher metabolic rate in the temporal
lobe and limbic system;
women have a more extensive corpus callosum and have higher metabolic activity in the cingulate gyrus;
other differences are found in the anatomy of the hypothalamus, thalamus and anterior commisure
- research is currently focusing on the functional significance of these differences
f. Conclusion
- with respect to early development the "mamawawa" hypothesis is clearly incorrect;
Everybody is born with a female program of development;
in normal males, the development of ovaries is overridden by H-Y antigen, and testes develop;
then the androgens released by the testes override the program for the development of female reproductive organs and brains, and the male equivalents develop
- hormone injections or gonadectomy at the appropriate stage of development can
produce individuals whose bodily sex is different from their genetic sex;
maleness and femaleness are but variations of the same, fundamentally female
program of development
Suggested Websites for Lecture 11a:
Gender and Brain: http://www.science.ca/scientists/Kimura/kimura.html
A biography of sorts of Doreen Kimura, highlighting her work on sex differences in brain function.
Sexual Disorders Related to Pituitary Dysfunction: http://medstat.med.utah.edu/kw/human_reprod/
The homepage of the Pituitary Tumors Network Association; see their links to hormonal imbalances and to sexual and reproductive dysfunction.
Behavioral Neuroendocrinology: http://www.sbne.org/
Homepage for the Behavioral Neuroendocrinology Society and its journal, Hormones and Behavior.
Lecture 11b -- THE EFFECTS OF SEX HORMONES IN PUBERTY AND ADULTHOOD
Outline
1. The Role of Hormones in Pubertal Development
a. Males
b. Females
2. Effects of Hormones in Adulthood
a. Males
b. Females
c. Anabolic Steroids
3. Androgenic Insensitivity Syndrome
4. The Hypothalamus and Sexual Behavior
5. Sexual Preference
1. The Role of Hormones in Pubertal Development
- At the beginning of puberty, there is a surge in the release of growth hormone and of both the gonadotropic hormones from the anterior pituitary
a. Males
- in males the surge in gonadotropic hormones increases the release of androgens from the testes
- this masculinizes the body and putitatively the brain; there is muscle development, body hair and pubic hair growth, lowering of the voice, the development of fertility, growth of sex organs, brain changes, etc.
b. Females
- in females the pubertal surge of gonadotropin release stimulates the release of estrogens from the ovaries
- this partially feminizes the body; estrogens stimulate breast growth, hip growth, onset of the menstrual cycle, fertility, etc.
- the growth of pubic hair and axillary hair (underarm hair) is stimulated by androstenedione, an androgen released by the adrenal cortex, thus the "mamawawa" stumbles again
2. Effects of Hormones in Adulthood
- hormones not only influence the development of the body and brain along male or
female lines, they play a role in activating the sexual behavior of men and women
a. Males
- the role of androgens in activating the sexual behavior of adult males is apparent following orchidectomy
- in about half the cases, there is a complete loss of ability to achieve an erection and of sexual motivation within a week or two of the operation; however, in other cases, the decline is less complete and/or more gradual; the reason for this variability is not understood
- castrated men also exhibit a variety of physical changes, e.g., reduction of body hair, deposition of fat on hips and chest, softening of the skin, a marked reduction of strength
- testosterone replacement injections restore sexual motivation, sexual potency, and remasculinize the bodies of orchidectomized males; but they remain sterile
- the fact that testosterone injections restore the sexuality of orchidectomized males has led to the view that the sexual motivation and performance of a male is determined by his level of testosterone, and thus that these can be increased in healthy intact males by testosterone injections
- this is NOT the case; in healthy intact males there is no correlation between testosterone levels and sexuality, and substantial increases (e.g., by injection) or decreases (e.g., by hemiorchidectomy) in testosterone levels have no effect on sexual motivation or performance
b. Females
- in female rodents, the 4 or 5 day menstrual cycle is correlated with a cycle of sexual receptivity (i.e., with an estrous cycle)
- in the day or two prior to ovulation, there is a gradual increase in estrogens, and a sudden surge in progesterone just as the mature egg is being released from its follicle
- during the next 12 to 18 hours the female is said to be in estrus: she is (1) fertile, (2) receptive, (3) proceptive, and (4) sexually attractive to male rats
- ovariectomy abolishes the estrous cycle; but ovariectomized female rodents can be readily brought into estrus by an injection of estradiol followed a day and a half later by an injection of progesterone
- human females are different; there is no clear-cut cycle of sexual receptivity associated with the menstrual cycle; ovariectomy eliminates vaginal lubrication, the menstrual cycle, and fertility, but it has no effect on sexual motivation
- according to one theory, the sexual motivation of human females is maintained by androgens; sexual motivation is lost following ovariectomy plus adrenalectomy, but is reinstated by replacement androgen injections; yet another slap in the face of the "mamawawa"
c. Anabolic Steroids
- testosterone has anabolic (growth promoting) effects, but it is not a particularly effective anabolic agent because it is quickly broken down in the body
- chemists have synthesized similar chemicals belonging to the same class (steroids) that are not broken down so quickly; these are the so-called anabolic steroids; there is currently an epidemic of anabolic steroid abuse among athletes
- although the early experimental evidence was ambiguous, there is clear evidence that anabolic steroids can increase the muscularity, strength, and performance of both male and female athletes
- however, there are a number of devastating side-effects: testicular atrophy and gynecomastia (breast growth) have been reported in men; amenorrhea, sterility, hirsutism (excessive growth of body hair), growth of the clitoris, masculine body shape, baldness, and deepening of the voice have been reported in women; in both men and women, there have been reports of muscle pain, muscle spasms, excessive water retention, blood in the urine, acne, nausea, vomiting, bleeding of the tongue, fits of anger, fits of depression, and cancerous liver tumors
3. Androgen Insensitivity Syndrome
- in order to understand the important role of androgens in male development, it is informative to understand what happens to males in the absence of their effects; for example, there are otherwise normal genetic males who suffer from the androgen insensitivity syndrome; they have normal levels of androgen but their bodies do not respond to it
- genetic males with androgen insensitivity frequently come to the attention of a physician when they become concerned about their inability to get pregnant; they are ostensibly happily married women
- a physical examination reveals:
(1) sparse pubic and axillary hair,
(2) they do not menstruate,
(3) they have shallow vaginas,
(4) they have internal testes and undeveloped male internal reproductive ducts,
and (5) their body cells are all of the normal male XY type
- How does this happen? Four steps appear to be involved:
(1) At 6 weeks, normal testes develop under the control of the Y chromosome.
(2) In the third month, testes release androgens, but normal female external reproductive organs (and presumably a female brain) develop because of the androgen insensitivity.
(3) Also in the third month, their female internal reproductive ducts degenerate (e.g., the inner one-third of the vagina) under the influence of Müllerian-inhibiting substance, and their male internal reproductive ducts do not develop because of their androgen insensitivity.
(4) At puberty, the low levels of estrogens released by the testes feminize the body because there are no offsetting androgen effects, but androstenedione cannot stimulate the female pattern of pubic and axillary hair growth.
- What treatment would you recommend?
Typically, neither the patient nor the husband is informed of the nature of the problem;
they are counseled to adopt;
the vagina may be surgically enlarged to eliminate pain associated with intercourse
4. The Hypothalamus and Sexual Behavior (use Digital Image CH11F02.BMP)
- the role of the hypothalamus in the control of the pituitary gland led to an examination of sex differences in the hypothalamus
- notably, the medial preoptic area in rats was found to be several times larger in males than in females
- at birth, the medial preoptic area is the same size in both sexes; however, within the first few days postnatal this area grows rapidly in males but not females. This growth is stimulated by estradiol, aromatized from testosterone; castration a day-1 postnatal reduces the size of the medial preoptic in adult rats.
- the size of the medial preoptic area has been correlated with testosterone levels and some aspects of sexual behavior; furthermore, stimulation elicits male rat sexual behavior. However, bilateral lesions of the area have only slight effects on male rat sexual behavior.
- in female rats, the ventromedial nucleus of the thalamus contains circuits critical to sexual behavior; stimulation elicits these behaviors, and lesions there reduce it. The VMN is critical to the onset of estrus in female rats, as microinjections of estrogen and progesterone there will bring on estrus. The VMN appears to act via a projection to the periaqueductal gray.
5. Sexual Preference
- many humans are not heterosexual; they are sexually attracted to members of the same bodily sex (homosexual), or to members of both bodily sexes (bisexual)
- many people believe that sexual preference can be changed by castration or hormone injections
- however, in females neither castration nor hormone injections influence the direction or intensity of sexual motivation
- in males castration greatly reduces sexual motivation, but replacement injections simply reinstates the original intensity and direction of sexual preferences
- it is believed that the neural circuits underlying sexual preference are permanently established early in life as the result of the interaction between hormones and experience; for example, perinatal castration of males or testosterone treatment of females induces same-sex preferences in a variety of species
- this is difficult to prove, however; the experiments necessary to test this hypothesis cannot be ethically performed on humans, and homosexuality and bisexuality are difficult to model in nonhumans
- LeVay (1991) found that the third interstitial nucleus of the hypothalamus is more than twice as large in heterosexual males than it is in heterosexual females and homosexual males; however, it is not clear whether this difference was a cause or a product of the homosexual preferences of his subjects
- more recently, Hamer et al., (1993) found that the concordance rate for homosexuality was 52% in monozygotic twins and 22% in dizygotic twins, suggesting that there may be a genetic basis for homosexuality. A gene implicated in male sexual preference has been located on the X-chromosome.
Suggested Websites for Lecture 11b:
Androgen Insensitivity: http://www.medhelp.org/www/ais/
A page devoted to androgen insensitivity syndrome.
Is Homosexuality Genetic? An Interview with Simon LeVay:
http://bewell.com/healthy/sexuality/1998/ga/index.shtml
From the Be Well site, an interview with Dr. Simon LeVay about his research into neuroanatomical correlates of homosexuality.
Sex, Flies, and Genes: http://www.sciam.com/0697issue/0697scicit4.html
Evidence that sexual behavior is under a certain degree of genetic control...at least in fruit flies! From the Scientific American's Science and the Citizen page.
How the Brain Organizes Sexual Behavior: http://www.epub.org.br/cm/n03/mente/sexo_i.htm
Another good link to the Brain and Mind e-magazine from the State University of Campinas, Brazil; a review of the physiology of coitus and the influence that the brain has on sexual preference and its control of sexual behavior.
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