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PSYC 342
Jens C Pruessner

PSYC 342 Lecture 7 - Jan. 31 Radioimmunoassay: Competitive Binding Assay The standard curve • Radioimmunoassay can be used with: • Blood samples Wednesday, 25 Jan•aSaliva samples • Some problems with the technique: Wednesday, 25 January, 12 • Dependency on specificity of the antibodies • If the receptor is not specific for a given hormone, it will bind to and thus detect other hormones from the same category that are not of interest Cross-reactivity with other hormones with a similar structure • Autoradiography: • A post-death assessment • Used to determine hormonal uptake and receptor location • Prepare target tissue (usually slices; stain half of them to highlight cellular structure) • Prepare hormone (radio label it) • Expose unstained tissue to hormone Expose hormone/tissue compounds to photographic film • • Develop film Pharmacological Techniques: • General agonists (mimic the administration of a certain hormone, but it is not released) and antagonists (prevent hormone from having anymore reaction by blocking hormone from binding to the receptor) • Receptor agonists and antagonists • Cannulation (connecting the blood system of two animals; animal A blood connect to animal B) Brain Imaging: • Positron Emission Tomography (PET) • Magnetic Resonance Imaging (MRI) • Functional Magnetic Resonance (fMRI) • Spectroscopy Genetic Manipulations: • Insertion of a gene not normally there (transgenic) • Removal of a gene not normally there (knockout) Sexual Determination and Behaviours: • Attribute major significance to the sex of our offspring • Labeling, social norms and rules • How do hormones cause the sexes to differentiate in terms of their morphology, physiology, and psychology Topic of High Controversy: Lawrence H Summers • • Sex and gender: two different terms • Sex is biological aspect; gender is societal and cultural aspect • How do hormones cause the sexes to differentiate in terms of their morphology, physiology, and psychology Historical Background: • Aristotle: epigenetic theory of sexual differentiation • Sex emerges during foetal and early life development • Primary and secondary sexual characteristics Primary sexual characteristics are the organs vital for reproduction, including genes • • Secondary sexual characteristics are the things that develop from puberty Sexual Differentiation Up To Puberty: • Chromosomal sex: men XY, women XX • Gonadal sex: men have testes, seminal vesicles, prostate gland and tubing; women have ovaries, uterus, oviducts • Hormonal sex: men produce a high androgen to estrogen ratio, women is the opposite • Morphological sex: men are larger and stronger • Sexual orientation: males are usually attracted to females, and vice versa Gender roles and gender identity: most people have the deep inner conviction that they belong to • the sex they possess (based on society and cultural factors) From Chromosomes to Gonads: • XX versus XY: genetic imprint • No different between the two during the first six weeks of development: bipotentiality • On the Y chromosome, there is the SRY gene (sex determining region of the Y chromosome), which produces the TDF (testis determining factor), a protein which will lead to the development of the testes from the germinal ridge • Blueprint of original sex is female unless Y chromosome is expressed • TDF stimulates Leydig cells to prevent the formation of the female genital tract from the Müllerian ducts • Happens through Müllerian Inhibitory Hormone (MIH) • High in males postnatally until puberty • No presence in females until puberty No SRY, no differentiation ➡ female • From Genitals to Sexual Development: • The testis, once determined, will then start producing sex-specific hormones which will lead the way to specific sexual development • Whole cycle only present in mammals • In reptiles, SRY is present but not critical; instead, temperature determines sex • Birds: Males have ZZ chromosome and females WZ (default setting male) Mechanisms of Hormone Action: • Testosterone has masculinizing effects through conversion to estradiol via aromatase Thus, estradiol has masculinizing effects! • • Estradiol absent in the developing female • Blocking aromatase blocks masculinization • (Exceptions are abundant: hyenas) Human Psychosexual Differentiation: • Babies at nine month capable of discriminating between the sexes • Children soon learn to identify their own gender, and understand that it is stable • Effect on gender roles and gender identity Sexual Differentiation at Puberty: • Period of relative hormonal inactivity during childhood • Dramatic surge of Hypothalamic hormones prior to and during puberty GnRH ➡ LH, FSH (from Pituitary) ➡ significant boost in production of sex steroid hormones • • Men: Leydig cells, testosterone Women: estrogen • • In addition: Adrenal cortex: DHEA, Androstenedione as puberty approaches • Six to seven in girls, seven to eight in boys • Growth spurt, acne, body odour Abnormal Sexual Development: Complete Androgen Insensitivity Syndrome • When the perfect woman is genetically male • Organism is not responsive to androgen; either receptors is not working, or they do not exert any effect from the androgen 15 Even though you produce testosterone, your body does not accept the hormones • • Your switching over from male sexual development to female sexual development; is sterile Inheritance of androgen insensitivity syndrome: Overview of androgen action on target cells Sex Differentiation Sex Differentiation of CAIS Patients: 18 20 Development of External Genitalia 21 Normal Male Development CAIS Development Wisniewski et al (2000) : - Looked at 14 women with confirmed CAIS Physical measurements at birth: - Determined from medical records. -CAIS babies appeared no different from unaffected infants in terms of birth weight. External genitalia was completely female with no abnormalities at birth for all participants. 24 Summary of Differentiation Summary of Differentiation: Puberty: • Pubertal feminization still occurs because: • Individuals with CAIS DO respond to estrogen The testis are a source of androgen, which is converted to estrogen • • Normal female secondary sex characteristics develop • Physical indicators of CAIS in adolescence: • Amenorrhea • No virilization despite normal to high levels of circulating testosterone Absence of post-pubertal axillary hair 25 • • Markedly decreased or absent pubic hair • Physical measurements in adulthood: • Women with CAIS tend to be tall and experience normal feminization of secondary sexual characteristics Aside from lacking female-typical amounts of axillary and pubic hair, the external female • genitalia of all participants appeared normal Treatment: • Current recommendation is removal of gonads after puberty • Because the individual will still respond to estrogen, if they have a source of androgen (the testis), it is converted to estrogen and normal female secondary sex characteristics develop • No treatment needed until mid-adolescence, unless malignancies develop (most of the time the condition is not known until puberty anyhow) • Testis are removed laparoscopically after breast development has occurred • The testis are moved after puberty because dysgerminoma is common among CAIS individuals (tumor development on the gonads) • Upon gonadectomy. ERT (estrogen replacement therapy) recommended • Transdermal estrogen (patch) or oral supplements • Aids in increasing and maintaining bone density • Supplement calcium and vitamin D DEXA scans (test for osteoporosis should be done early in diagnosis, and can be treated • by biophosphonate therapy, although treatment of the method is controversial • What happens if gonads are removed before? • Puberty can be induced with exogenous hormones, estrogen, normally around the age of twelve, although there are side effects to this treatment After gonadectomy, the individual must take hormonal supplementation of estrogen • • Counseling and psychotherapy are an INTEGRAL part of dealing with the mental and emotional aspects of the condition • Surgical creation (in which dilation will still be necessary after sugary to prevent scarring and vaginal stricture) • Vaginal dilation - can be quite painful, and uncomfortable emotionally and physically for young girls. Creating length is the priority, afterwards, attempts are made to create width • Dilation is recommended before surgical creation • Dilation must be done for at least half and hour per day PSYC 342 Lecture 8 - Feb. 7 Gender Identity: • Sex refers to the biological sex Gender refers to the psychological sex • • Factors influencing gender identity: • Biological factors (genes, hormone exposure) • Environmental factors (society, cultural, and parental influences) • The interaction between the two • Gender identity refers to an individual’s basic sense of self; as being either male or female What is Klinefelter Syndrome (KS): • Trisomic Anomalies: 47 XXY chromosome • Instead of having the usual XY chromosome, males have an extra X in their cells • Note: Not every male with XXY chromosomes has KS. XXY males are however at risk to developing KS • Physical, endocrinologic, reproductive, cognitive, and behavioural disabilities This affects males over their development • Prevalence: • Between 1 in 500 and 1 in 1000 males • 0 females • Other variants of Klinefelter syndrome: • 1 out of 50,000 males • The cause of XXY syndrome is not clear • Pregnant women over 35 years old will slightly increase the risk of the XXY chromosome • KS is NOT an inherited disorder • During meiosis, the 46 chromosomes divide into 2 new cells of 23 chromosomes each • In female, each cell gets a X • In male, one cell gets the X and the other gets the Y For XXY, there is an error during the formation of the reproduction cells, which results in an • additional X. This is called non-disjunction • The XX or the XY chromosomes failed to exchange genetic material • Hence producing a XX egg or a XY sperm when it is supposed to be X or Y only Prevalence*  The$XX$or$the$XY$chromosomes$failed$to$exchange$  genetic$material.$ Between 1 in 500 and 1 in 1000 males  Hence$producing$a$XX$egg$or$a$XY$sperm$when$it$is$ supposed$to$be$X$or$Y$only.$  0 female  Other variants of 1. The&XY&sperm&comes&in&contact& Klinefelter syndrome: with&a&normal&X&egg. 2. The&normal&Y&sperm&gets&in&the& XX&egg.& " 1 out of 50,000 males • In&both&cases,&it&will&result&in&a& XXY&abnormality.& 32 Physical Symptoms: 32 35 • Not all males with this condition have the same symptoms or to the same degree. Symptoms depend on how many cells are affected, the amount of testosterone, and the age when the condition is diagnosed Effects on Physical Development: • As infants: • Reduced strength • Sit-up, crawl, and walk later than other infants • Weak muscles • After age 4, tend to be taller and have less muscle control and coordination Physical Symptoms: • Do not make as much testosterone (hypogonadism) • Incomplete virilisation • Can have normal sex lives, but they make little or no sperm • Infertile • Penis does not reach adult size • Small firm testicles (microorchidism) • Enlarged breasts (gynecomastia) • Less facial and body hair • Less muscular body (underdeveloped muscles) • Pear shaped (long arms and legs, narrow shoulders, broad hips) • Taller (long legs) • Weaker bones Effects on Health: • Increased risk of: • Autoimmune diseases • Breast cancer • Cardiovascular disease • Diabetes mellitus • Extragonadal germ cell tumours • Lung disease • Osteoporosis • Tooth decay • Vein diseases Cognitive and Psychological Problems: • Difficulty in reading, understanding words, finding words, verbally expressing their thoughts and auditory memory Intelligence: They are not mentally challenged • • IQ within normal range • Verbal IQ < Performance IQ • Lower verbal IQ related to • Language deficits Gender Identity: • Androgynous or feminine feelings that can develop at an early age • Some consider themselves to be transgendered or intersexed • Transitioning to live as women Testosterone Treatment: • Androgen replacement should being at puberty • Early treatment: • Promotes normalization of the body or development of secondary characteristics (i.e. Facial hair, increase muscle mass, wider shoulder, etc. • May improve behaviour and work performance • Reduces the risk of osteoporosis, autoimmune diseases and breast cancer History of XYY Syndrome: • XYY was first discovered in 1961 by Dr. Avery A. Sandberg Incidental finding: 44 years old man was karyotyped because he had a daughter with Down • Syndrome • 47, XYY was the last of the common sex chromosome abnormalities to be discovered Prevalence of XYY Syndrome: • The incidence is reported to be 1 in 1,000 males • 80-90% of the time will be 47, XYY • 10-20% of the time, 46 XY/47, XYY; also known as mosaic • May be diagnosed both prenatally and postnatally Non-Disjunction in Meiosis II: • 47 XYY syndrome arises from postzygotic mitotic error or non-disjunction during meiosis II • Prime illustration of the most common origin of this syndrome • Found that in over 84% of cases, the additional Y chromosome was generated by non-disjunction at paternal meiosis II, after a normal meiosis I Implications of XYY: Further individual factors, which have the potential to be affected by this syndrome include: • • Physical attributes • Height • Psychological and cognitive • Intelligence • Behavioural • Aggression • The XYY man is not characterized by distinct or unusual physical features; however, XYY males have been found to exhibit the following: Taller stature • • Thinner build • Increased acne • Skeletal disfigurement (in rare cases) • XYY males are similar to XY males in that: • Quality of life is not affected by the syndrome • Life space Puberty appears at the expected time • • Physical sexual development • Sex organs • Secondary sex characteristics • Hormone levels • Testosterone XYY Low IQ? • IQ scores are slightly lower by 10-15 points (lower limit of normal range) • Scores lower than their siblings IQ → combination of gene and environment - ‘reaction range’ • Learning Disability: • XYY boys → lower scores on differential abilities scale and measures of language & academic achievement • XYY males perform lower on reading tests, rapid naming test, and in areas such as semantics, syntax, pragmatics, and expressing and interpreting intent • Difficulty understanding figurative language, as well as oral expression, have weak verbal memory • Have difficulty mastering material in school & need more time to learn compared to other students Inside the XYY Brain: • Learning and language disabilities → 50% of XYY Karyotype males • Learning difficulties • Language reading • XYY boys have mild generalized cognitive impairment, with impaired language abilities (Reading and Spelling) XYY Male’s Motor Function: • XYY males also suffer from a lack of coordination Study by Ross, Zeger et al (2009) → motor function was examined using fine motor and gross • motor tasks as well as measures of strength, speed and agility, coordination • The XYY group → performance on complex motor tasks were not as well as the controls • This impairment results in less athletic ability and leads to further problems XYY and Aggression: • Study by Jacobs et al (1965) • Research question: Will an extra Y chromosome predispose its carriers to unusually aggressive behaviour? • Setting: Maximum security hospital in Scotland Study type: Chromosomal survey on 192 males • • Results: 9 XYY males were found, 3.5% of the original sample • Conclusion: XYY males are overrepresented in these types of institutions, therefore these men might be more aggressive and violent Biases in Early Studies: • Small samples with inadequate control groups • Based on single cases of extreme antisocial behaviour • Sampling coming from populations considered likely to have a high proportion of XYY men (ex: prisons or maximum security hospitals) • XYY or XY identity known to researchers assessing subjects’ personalities Treatment: • There is no treatment for XYY, and since research has not found significant adverse effects, there is no need for one Comorbid disorders that are treated individually • • Acne • Skeletal disfigurement • ADD • Language disabilites • Antisocial personality disorder Summary: • Physically, XYY males do not differ significantly from XY males • XYY males may have temper tantrums and conduct problems They may have learning disabilities and problems with language as well • • Self esteem might be impaired due to their unusual height and acne, both of which can cause distress to an adolescent • These characteristics, when combined with lower IQ can lead to increased criminality • However, the crimes committed tend to be against property and are not generally aggressive • Proper treatment of the associated factors of XYY allows these men to lead normal lives Congenital Adrenal Hyperplasia (CAH): • CAH affects about 1% of the population • CAH is an autosomal recessive genetic disorder: both abnormal genes are necessary for the disease to manifest itself • Most common form of CAH is due to a 21-hydroxylase deficiency • Spectrum disorder affecting adrenal glands • The adrenal glands are located above the kidneys • The pituitary gland regulates the production of hormones in the adrenal glands • Two main parts of the adrenal glands: • Adrenal Medulla • Adrenal Cortex • The adrenal cortex is the part of the adrenal glands affected in CAH • The adrenal cortex produces 3 types of hormones: • Cortisol • Steroid hormone • Helps deal with physical and emotional stress • Maintains adequate energy supply and blood sugar levels Aldosterone • • Steroid hormone • Maintains normal levels of sodium and potassium • Maintains normal blood volume of the body • Androgens • Male steroid hormone (hormone that is affected) • The root cause of CAH is a deficiency of the enzyme 21-hydroxylase (21-OHD) in the adrenal cortex • 21-OHD is necessary for the production of cortisol and aldosterone The problem with CAH is that the 21-OHD deficiency eventually causes a deregulation of the HPA • axis leading to the various symptoms and health problems associated with CAH • The pituitary gland, sensing a lack of cortisol in the bloodstream (caused by 21-OHD deficiency), releases ACTH (adrenocorticotropic hormone) • For 17-hydroxyprogesterone (17-OHP) to be converted into cortisol, 21-OHD is necessary • No 21-OHD = No cortisol • The root caus• Adrenal glands are unable to produce cortisol 21-hydroxylase (21-OHD) in the adrenal cortex. • Pituitary gland keeps releasing ACTH sensing cortisol levels are too low • This leads to an overabundance of 17-OHP in the adrenal glands • This excess gets converted to androgens instead of cortisol • 21-OHD is necessary for the production of cor4sol • Androgens can be produced because they do not need 21-OHD to be produced and aldosterone. The problem with CAH • is that the 21-OHD deficiency eventually causes a deregulation of the HPA axis leading to the various symptoms and health problems associated with CAH. • Problems of those with CAH are threefold: Monday, 6 February, 12 • Very little or no production of cortisol Often accompanied with low or no production of aldosterone • • Side-effect: overproduction of androgens • Hyperplasia: Enlarged adrenal glands • Severe form of CAH is called ‘Classic Congenital Adrenal Hyperplasia’ • Mild form of CAH is called ‘Non-classic Congenital Adrenal Hyperplasia’ • The most common form if 21-hydroxylase deficiency which accounts for 95% of the cases • The second most common form of CAH is 11-hydroxylase deficiency • Non-classical CAH is a variation of CAH that can commence anywhere from early childhood to early adulthood Symptoms: • Premature development of pubic hair • Advanced bone age • Severe acne • Childhood body odor • Oily hair and skin • Depression • Anxiety Symptoms usually commence shortly after the onset of menstruation • • Thinning of hair on head and infertility • Facial hair that is dark and course on the upper lip and chin • The menarche could be normal or delayed but there tends to be menstrual irregularities • Formation of ovarian cysts due to the disruption of the gonadotropin release and its effects on the ovaries Symptoms in Men: • Similar to men having XYY; nothing too dramatic • Acne • Growth spurts Early beard growth • • The testes are usually small compared to the phallus • Low sperm count • Short stature Symptoms in Women: • Ambiguous genitalia in girls • Enlarged clitoris • Joined labia folds • Females born with CAH have XX chromosomes and normal internal female genitalia. The abnormality lies in the external genitalia. The abnormality lies in the external genitalia when the hormones kick in that relates to the further development of your sexual characteristics (secondary sexual characteristics) Gender Identity Relevance: • Childhood/Adolescence: • Increase in testosterone levels/increased male typical play (e.g. Desire male careers) • More aggressive • Less interested in marriage, motherhood, feminine appearance (jewellery, makeup) than controls • Lower levels of empathy, intimacy Less heterosexual activity • • Homosexual fantasies and increased occurrence of homosexuality and bisexuality • CAH > NCAH > control • Gender identity is ambiguous • Rank themselves somewhere in between typical girls and tomboys • Hormones can affect our gender identity even if our genetic composition is of an original sex Treatment: • Main goal: provide glucocorticoids to reduce excess CRH and ACTH • Mineralocorticoids for salt-wasting form or not, e.g. Fludrocortisone • Hydrocortisone: infancy, childhood • Dex/Prednisone: adolescents, adults (bedtime dose) Guevedoces: • Translated as ‘penis with twelve’ • Genetically born males with enzyme deficiency are raised as girls and establish female gender identity • By the time they reach puberty and their bodies become masculinized, they change their gender identity from female to male Monday, 6 February, 12 Monday, 6 February, 12 • There is an interaction of early hormone exposure and parental/environmental influences on gender identity • Since the factors are confounded, individual influence is difficult to establish Gender Dysphoria: • XX or XY chromosomes • Male or female feels strong identification with the opposite sex • Feel as if trapped in the body of the opposite sex Symptoms: • Belief that they will grow up to be the opposite sex • Expressed desire to be of the opposite sex • Disgust with their own genitalia
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