3_3_08_Reproductive__Physiology_Hormones

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Unformatted text preview: Clicker Question An erection results from: A) B) C) D) E) the release of nitric oxide (NO) near the arteries in the penis by the parasympathetic nervous system. NO­induced dilation of the arteries that bring blood into the penis. swelling of the corpus cavernosum. swelling­induced blockage of the veins that take blood out of the penis. all of the above. Where are we? Last time I covered… Reproductive biology of men and women. Today I will cover… What makes one a man, a woman, or an intersexual? (The definition of sex, like the definition of life, is not as clear as one may expect.) Environmental estrogens. Contraception. Before the Discovery of Sex Before Chromosomes, it was Relatively Easy to Tell the Boys from the Girls to Prince Albert and Queen Victoria The Male and Female Phenotypes The were Distinguished by the Genitalia Males had a penis; females had a vagina. Chromosomal Sex You probably learned that humans have 23 pairs of chromosomes. One pair, composed of the X and Y chromosomes, determines whether one is male or female. The mother, with her diploid (XX) germ cells, typically produces eggs that are all X and the father, with his diploid (XY) germ cells, typically produces sperm that are either X or Y. A zygote with XX chromosomes will typically develop into a female, and one with XY chromosomes will typically develop into a male. E. B. Wilson and Nettie Stevens The Chromosomal Basis of Sex E. B. Wilson and Nettie Stevens noticed that in many animals there were two accessory chromosomes. These chromosomes did not look like each other the way other chromosomes in a homologous pair looked like each other. They were later called X and Y chromosomes. The testicular cells that gave rise to sperm had both the X and Y chromosomes. The ovarian cells that gave rise to eggs had two X chromosomes. They concluded that the presence of a Y chromosome determined maleness and the absence of a Y chromosome determined femaleness. Sex is Determined by Chromosomes This was the first evidence that one of the hereditary traits that determine our uniqueness was carried by chromosomes. The sperm determines the chromosomal sex of the zygote. Zygotes that get a Y chromosome from the sperm become chromosomally male and zygotes that get an X chromosome from the sperm become chromosomally female. Chromosomal Male and Chromosomal Female The Unequal Distribution of Chromosomes (NonDisjunction) During Anaphase II of Meiosis Reenforces the Role of the Y Chromosome in the enforces Determination of Sex Determination Individuals with no Y chromosome (X­, XX or XXX) develop into females. Individuals with one Y chromosome (XY, XXY, XXXY or XXXXY) develop into males. This indicates that something on the Y chromosome causes an individual to develop into a male. Chromosomal Sex Embryos with XY chromosomes typically develop into males and embryos with XX chromosomes typically develop into females. But the phenotypic sex is not always correlated with the chromosomal sex. Cis-Sexuals and Trans-Sexuals Male Female We could make two columns of characteristics: one that defines a male testes ovaries and another that defines a penis vagina female. XY XX Having all of the high estrogens characteristics that are in high androgens one column and none of androgen sensitivity the characteristics that are in the other columnresults in a cis­sexual. Having characteristics from both columns makes one a trans­sexual, also known as an intersexual. Chromosomal Sex Does Not Always Chromosomal Define Phenotypic Sex There is a small possibility that a person can have two X chromosomes (XX) and be male in all other regards. If certain segments of the Y chromosome are broken off and transferred to another chromosome or transferred to the X chromosome during meiosis, the phenotypic sex can differ from the chromosomal sex. This means that sex is determined by more than just the type of sex chromosome an individual has. The Phenotype Depends, in Part, The on the Genotype on The phenotype is the outward appearance of a trait (e.g. male or female). The genotype is the combination of heritable materials (alleles made of DNA) that have the potential to code for the trait in question. How is Genetic Diversity Generated? Mutation (nucleotide change in DNA)—a mutation produces a new allele. An allele is a variation of a gene. Independent Assortment is the random mixing of the maternally­ derived and paternally­derived chromosomes in an individual. Recombination (crossing over during meiosis) produces different combinations of the alleles of various genes (e.g. hair and eye color)—it is like shuffling cards. As a Result of Mutations, Homologous As Chromosomes Carry Different Versions (Alleles) of Genes (Alleles) Meiosis Can Introduce Variability Meiosis (Individuality) in All Traits (Individuality) The independent orientation of the pairs of homologous chromosomes during metaphase I of meiosis makes it possible for the gametes you produce to differ from the gametes that created you. Your Gametes Are Not Like Your Your Mother’s Nor Your Father’s Gametes Mother’s As a consequence of independent orientation, the total number of chromosomal combinations that can be created in the gametes is 2n, where n is the haploid number of chromosomes. In humans, where n = 23, there are 223 or 8,388,608 different possible gametes based on independent orientations alone. Children by Kahlil Gibran They come through you but not from you, And though they are with you, yet they belong not to you. You may give them your love but not your thoughts. For they have their own thoughts. Your children are not your children. They are the sons and daughters of Life's longing for itself. Crossing Over or Crossing Recombination Further Increases Genetic Variability Variability Chromosomal Sex vs. Gonadal Sex The presence or absence of a Y chromosome typically makes one chromosomally male or female, respectively. There is a particulate factor on the Y chromosome that determines whether an embryo will develop testes or ovaries and become gonadally male or female. Up until 6­7 weeks in the womb, the gonadal sex of the embryo is undetermined and the testes and ovaries exist as undifferentiated gonads. Six Weeks: The Undifferentiated Six Reproductive System Reproductive The developing embryo (XX or XY) contains undifferentiated gonads and has the potential to be either male or female. It also contains two systems of genital ducts. The Mullerian ducts can differentiate into the fallopian tubes, uterus, and vagina. The Wolffian ducts can differentiate into the epididymis, vas deferens and seminal vesicles. Development of the Female Development Reproductive System Reproductive In the absence of a Y chromosome, the gonads stay in place and differentiate into ovaries. The Wolffian ducts degenerate. The Mullerian ducts continue to differentiate into fallopian tubes, uterus and the vagina. The female developmental program does not require any embryonic hormones, just the absence of male hormones. Development of the Male Development Reproductive System Reproductive In the presence of a Y chromosome, the gonads differentiate into testes, which produce testosterone. The testosterone prevents the disintegration of the Wolffian ducts and allows them to differentiate into the epididymis, vas deferens and seminal vesicles. The testes also produce a hormone known as the Mullerian inhibiting factor (MIF), which causes the destruction of the Mullerian ducts. Development of Genital Ducts in Development Gonadal Males and Females Gonadal Testosterone, Androgens and Other Steroids Are Synthesized from Cholesterol arbl.cvmbs.colostate.edu/hbooks/pat hphys/endocrine/basics/steroidogen esis.gif Phenotypic Sex: The Fate of the Phenotypic Undifferentiated Phallus Undifferentiated Before the testes start producing testosterone and other androgens, all embryos look female from the outside. They have a vulva­like opening, labia­like folds and a small undifferentiated phallus. In the 7th ­12th week, androgens cause the undifferentiated phallus to become the penis in a male. Without androgens, the undifferentiated phallus becomes the clitoris in a female. External Genitalia: Labia Majora and External Scrotum Scrotum The labioscrotal swelling becomes the labia majora, the entrance to the vagina and the exit for the urethra in a female. In males, it fuses to form the scrotum and consequently, a new urethra exit must be formed. External Genitalia 12 Week th The urethra in the female naturally exits through the labia. However, in males, when the labioscrotal swelling fuses to form a scrotum, a new urethra is formed from the bladder to the tip of the penis. The gonads are formed near the kidneys. In order to produce sperm at the requisite temperature (94 °F), the testes must descend from the abdominal cavity (98.6 °F) to the scrotum. The gonads are initially held in place by the suspensory ligament, which holds them near the kidney and the gubernaculum, which pulls them toward the scrotum. The testes produce insulin­like­hormone­3, which strengthens the gubernaculum which causes it to pull the testes to the scrotum. Testosterone weakens the suspensory ligament which facilitates the downward movement. The Testes Descend Into the The Scrotum (2-9 Months) Scrotum The SRY Gene Causes Male The Development Development In the 1990s it was discovered that in 0.005% of babies, the males had XX chromosomes and the females had XY chromosomes. The Y chromosome in the XY females had a piece missing and the X chromosome in the XX males had an extra piece. The gene on the region of the chromosome that contained the testes determining factor was named sry, which stands for Sex­determining Region on the Y chromosome. How do we know that the sry gene How determines the sex of the baby? determines Female mice do not have the sry gene. Male mice do have the sry gene. It is turned on in the gonad for only a couple of days. If the sry gene is damaged, XY mice become females. If the sry gene is put into XX mice, they become males. The sry gene is a master switch sry seems to be the master switch that triggers the events that convert the embryo into a male. Without the sry gene, the embryo develops into a female. It appears that femaleness is the "default" program, which makes sense since the embryo is developing in a woman’s body, flooded with estrogens. How does the sry gene cause the How gonads to become testes? gonads Sry seems to turn on or off several genes that result in the differentiation of testes. Steroid Hormones and Puberty The ovaries and testes are endocrine glands that produce three classes of steroid hormones: estrogens, progestins and androgens. These hormones induce puberty, which is the time an individual becomes capable of reproducing. Typical females have high ratios of estrogens to androgens. Typical males have high ratios of androgens to estrogens. Puberty: Androgens Cause Androgens Secondary Sex Characteristics to Secondary Develop in Males Males increased bone growth, appetite and muscle mass, which results in broad shoulders and chests a prominent Adam's apple and deeper voice due to lengthened larynx pubic, facial, chest and abdominal hair; baldness exaggeration of preexisting patterns of aggression Puberty: Estrogens and Other Estrogens Hormones Cause Secondary Sex Characteristics to Develop in Females Characteristics Females enlarged breasts with functional mammary glands menstrual cycle pubic and underarm hair subcutaneous fat wider hips than shoulders smooth skin texture Anabolic Steroids Corticosteroids, like cortisol are catabolic steroids that cause the breakdown of muscle tissue. Androgens are anabolic steroids that stimulate appetite and induce the build­up of muscle tissue. Anabolic steroids at high levels in the body will be converted to estrogen, thus blurring some distinctions between men and women. The sexual side effects of anabolic steroids use include men developing breasts and a lower sperm count and women developing body hair and a deeper voice. The Senate Has an Interest in the Illegal The Use of Anabolic Steroids by Athletes Use http://www.drugfreesport.com/choices/drugs/steroids.html The Production of Sex Steroids in The Males and Females is Regulated by the Hypothalamus and Anterior Pituitary Hypothalamus The hypothalamus synthesizes and secretes “releasing hormones” that travel to and stimulate the anterior pituitary. The stimulated anterior pituitary synthesizes and secretes Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH). LH stimulates the production of sex hormones by the ovaries and testes. FSH stimulates the production of eggs and sperm. Control of Sex Hormones Post Pubescent Hormone Levels in Post Males are Constant Post-Pubescent Hormonal Levels Post-Pubescent in Females Cycle in In females, FSH stimulates the growth of the ovarian follicle. As the follicle grows, it secretes more and more estrogen. The estrogen level peaks when the follicle is mature. High levels of estrogen stimulate the hypothalamus to secrete more releasing hormones which causes the anterior pituitary to secrete massive amounts of FSH and LH. The high levels of FSH and LH induce ovulation. High levels of LH also induce the corpus luteum to secrete estrogen and progesterone. The high levels of estrogen and progesterone cause the pituitary to stop secreting FSH and LH. Hormone Levels Cycle Monthly in Hormone Females Pregnancy stops the cycle because the secretion of hCG by hCG the chorion causes a continued secretion of progesterone and progesterone estrogen by the corpus luteum. The high levels of progesterone and estrogen inhibit ovulation and prevents the sloughing off of the endometrium (menstruation). endometrium Birth control pills release high enough levels of estrogens and progestins to prevent ovulation. progestins Hormones and Behavior Singing is a secondary sex characteristic in canaries. The males sing and the females do not. Sam Leonard (1939) injected testosterone into female canaries and they started to sing like males. Perhaps, in general, sex hormones regulate “sex­ specific behaviors”, but the evidence is not clear. Reproductive Hormone Oxytocin Reproductive and Behavior and Oxytocin, a hormone secreted by the posterior pituitary, triggers contraction of the uterus during childbirth and caused the mammary glands to secrete milk during nursing. Oxytocin is produced in both males and females during orgasm. Oxytocin reduces stress and increases trust and bonding between people. The Male-Female Continuum The Males and females are not necessarily qualitative opposites caused by having XX or XY chromosomes. There is a male­female continuum that makes sex identity, in a small portion of the population, a somewhat quantitative and continuous characteristic. Intersex refers to mismatches in the sex chromosomes, the gonads, the genitalia and the secondary sexual characters. isna.org ukia.co.uk intersexinitiative.org What is a Male or a Female? Occasionally XX people are males because a translocation of the gene has placed the sry gene on one of the X chromosomes. XY women may have a mutant form of sry. XY intersexuals may have normal sry and a mutation in another gene that makes them insensitive to androgens. ais aissg X Androgen Insensitivity Males and females usually have at least one X chromosome that contains a gene that codes for an androgen receptor that makes their body sensitive to androgens. If this gene has a mutation that leads to complete androgen insensitivity, a child will have male internal organs but develop female genitalia and secondary sex characteristics. In partial androgen insensitivity (1/4500), the child will be born with ambiguous genitalia and secondary sex characteristics and may be brought up as either male, female or intersex, depending on the condition. Dihydrotestosterone (DHT) Dihydrotestosterone is a more potent androgen that testosterone. The enzyme that converts testosterone to dihydroxytestosterone is 5­ alpha reductase . A 5­alpha reductase deficiency in an XY person results in an androgen disorder characterized by a female phenotype or a severely underdeveloped male phenotype. Another Way to Become an Another Intersexual: Adrenal Hyperplasia Intersexual: • • A person with adrenal hyperplasia has an enzyme deficiency that leads to the underproduction of cortisol and aldosterone and the overproduction of androgens. XX individuals can be intersexuals if they overproduce androgens as a result of adrenal hyperplasia. transgenderzone.com There are Many Ways to Form There Intersexuals Intersexuals A mutation in any of the enzymes that convert testosterone to dihydrotestosterone or testosterone to estradiol may result in intersexuals. Female Individuality Male Individuality A Phallus—Intermediate Between a Phallus—Intermediate Penis and a Clitoris External Genitalia—Intermediate External between a Scrotum and a Vulva Gender Verification in Sports In the early 1960s, there were rumors that men were secretly posing as women to complete in the Olympics. In 1966, female athletes disrobed and their genitals were inspected at the European Track and Field Championships in Budapest, and gynecologic examinations were performed at the Commonwealth Games in Jamaica. Complaints and resentment about this embarrassing approach led the International Olympic Committee (IOC) to search for an alternative gender verification method at its competitions. In 1968, at the Mexico City Summer Olympics, the IOC required all female athletes to undergo sex chromosome analysis. Gender Verification in Sports In 1992, at the Albertville Winter Olympics, gender was verified by SRY testing. 8 out of 3387 female athletes were found to be SRY positive and 7 of the 8 had complete or partial androgen insensitivity. The other SRY­positive female athlete was a gonadectomized woman who probably had 5­alpha reductase deficiency. Now the athletes must urinate under the watchful eyes of the Olympic Committee to test for drugs that give athletes an unfair advantage. At the same time, males and females are distinguished, as they were in the Victorian era, by their external genitalia. Gender verification unfairly excludes women who had a birth defect involving gonads and external genitalia. The IOC has recognized that there is a continuum between males and females and it is a hard to decide where the cutoff is using laboratory techniques. Body-Sculpting Spandex Makes Body-Sculpting Gender Verification Unnecessary Gender Gender verification is no longer needed to achieve its original purpose of detecting male impostors because of the revealing, body­sculpting apparel worn by modern athletes. 'There's no way with today's spandex uniforms that someone would mistake a male masquerading as a female.' Gender Identity One’s sexual identity is an important aspect in a person’s self identity. While the concept of two sexes is important for reproduction, it is limiting in terms of the sexual identity of some people. It is only fair to help people find their sexual or gender identity by reducing the secrecy, stigma and taboo nature of disorders in sexual development (DSD). Variations in genes result in a broad spectrum of sexual intermediates between males and females. I have only talked about the genes involved in the biological determination of sexual identity. Are there alleles that cause us to think, act or dress like a stereotypical male or stereotypical female? gannett.cornell.edu­LGBTQ Robert Latou Dickinson (1933) “When the time comes that diagrams and descriptions of the normal functions of these universal organs are as generally accessible and as much taken for granted as are pictures of other life processes, we shall doubtless wonder at our artificially fostered mystifications and many of our elaborately manufactured attitudes of shame….” Environmental Hormones Environmental Carlos Sonnenschein and Ana Soto were studying cell division. Estrogen causes culture cells to divide and they were looking for the natural inhibitor that put a stop to cell division. All of a sudden all their control cells, which were not given estrogen, continued to divide. What was causing the cells to divide? A Mystery Solved It turned out that Corning had changed the recipe they used to make plastic tubes and it was something in the new tubes that caused cell division. Corning would not tell them the name of the new compound used to make the plastic, since it was a trade secret. Sonnenschein and Soto discovered what the chemical was that was leaching from the plastic of the new tubes. It was nonylphenol, which is a synthetic estrogen, similar to the estrogen nonoxynol­9, used in contraceptives. Other Environmental Estrogens Thalates: plastics industry Alkylphenols (nonylphenol): detergents Bisphenol A: Used to coat foods and in dental sealants Lindane: pesticide used on cereals, soft fruits, cabbage Vinclozolin: fungicide used on foods Dioxins: used in paper production leaches from transformer disposal Phytoestrogens: soy products Estrogens: estrogens from birth control pills, rings etc., and hormone replacement therapy that are eliminated in the urine. Male Fertility and Environmental Male Estrogens Estrogens In many places throughout the world, male fertility is declining. One factor correlated with declining semen quality (concentration of sperm, % normal morphology, % motile) is environmental estrogens. However, the decrease in semen quality may be caused by many environmental, behavioral, nutritional and developmental factors, including environmental estrogens. Human Sperm Suppression From the Study of Scottish Male Reproductive Health www.link.med.ed.ac.uk/ HEW/repro/default.htm Environmental Endocrine Disruptors Environmental and the Increase in Intersexes? and There is a high proportion of intersex fish in populations living downstream from waste treatment plants. There is a reduction in penis size and testosterone levels in alligators living in Florida. Female alligators have estrogen levels that are two times higher than normal— both effects are probably due to a breakdown product of the pesticide DDT. Testing Who should be the guinea pigs for testing new drugs (e.g. birth control pills) or the effect of toxins (e.g. alkylphenols) on reproductive health? Should animals be tested before humans? If so, which animals? If Alexander Fleming had used guinea pigs to test the effectiveness of penicillin, we probably would not have penicillin today because guinea pigs are killed by tiny doses of penicillin during certain times of the year. When should people be used for tests? Under what circumstances would you volunteer for a test? http://www.cancer.gov/clinicaltrials/conducting/informed­consent­guide/page4 Law of Malthus The food supply grows arithmetically and the population grows geometrically. We must ensure that there is enough food for each person. We have discussed methods to increase the food supply. There are a number of methods that reduce the chance of conception and an unwanted pregnancy. Depending on your views of when life begins, there are various methods that prevent birth. Some Methods for Separating Some Sex from Fertilization Sex Behavioral Surgical Abstinence (no intercourse) Elimination of rape Homosexuality Tubal ligation (fallopian tubes tied) Vasectomy (vas deferens cut) Diaphragm Condom Physical Barrier Chemical Hormonal Oral contraceptives Spermicide Vaginal ring Contraceptive patch Contraceptives www.soc.ucsb.edu/sexinfo/ Intrauterine Device (IUD) Ernst Grafenberg (1927), who the “G spot” is named after, was interested in the medical emancipation of women. He designed an intrauterine ring made out of “German Silver” wire, which contained 26% copper as a contraceptive. There are many modern designs and each one has a string that indicates that the IUD is in place. Dalkon Shield There is normally no bacteria in the uterus, fallopian tubes and ovaries. In most IUDs, there is a single monofilament string that goes between the IUD in the uterus and the vagina. The Dalkon Shield had a multifilament string that acted as a wick and pulled bacteria from the vagina into the uterus. The bacteria, including Chlamydia and Gonorrhea caused pelvic inflammatory disease (PID) which can destroy the ovaries, causing sterility and the fallopian tubes causing ectopic pregnancies. www.cdc.gov/ Intrauterine Devices (IUDs) The Dalkon Shield was the only IUD that had a multifilament string. All other IUDs have a monofilament string and have a low risk of causing PID. ParaGard is one modern hormone­free version of the IUD. Mirena is a modern IUD that contains progesterone which reduces menstrual bleeding. mirena paragard.com www.cdc.gov Advertising by the Pharmaceutical Company Advertising Influences Our Common Sense Influences Critical Thinking and Making Decisions Critical with Incomplete Knowledge with The Dalkon Shield experience gives IUDs a bad name to this day. IUDs are the most effective form of contraception for people who have sex (99.4% effective). (Abstinence is the most effective form of contraception for people who do not have sex). IUDs are the most widely­used form of contraception worldwide. Critical Thinking and Making Decisions Critical with Incomplete Knowledge with An IUD is a reversible form of contraception and can last up to 10­12 years, making it the most inexpensive form of contraception. IUDs increase the possibility of getting an infection that leads to PID and women who have a high risk of getting vaginal infections should not use IUDs. IUDS do not protect against sexually­ transmitted infections (STIs). It is important to check the string because IUDs can be expelled from the uterus without the woman knowing. Male Birth Control Pill Frances Platt noticed that men treated with N­ butyldeoxynojirimycin (NB­DNJ, Zavesca), a drug that was being tested for treating Gaucher’s disease, became temporarily infertile. She then began to test the drug on mice and found that it reversibly inhibited sperm development, making the mice infertile. Unfortunately, clinical trials show that it does not work on humans. http://www.malecontraceptives.org/ Use Your Head When it Comes to Use Sex Sex http://www.soc.ucsb.edu/sexinfo/ Date Rape Drug Date Test Strips and Coasters Coasters http://www.drinksafetech.com/products.php Informed Consent Informed Informed consent is a legal condition in which a person gives his/her consent based upon an appreciation and understanding of the facts and implications of an action. The individual needs to be in possession of all of his/her faculties. To give informed consent, a person cannot be without an impairment of judgment at the time of consenting. Such impairments include intoxication, drunkenness and using drugs. Make all your important decisions based on informed consent. Emergency Contraception (e.g. Plan B) can be used within 72 h after unprotected sex and prevents ovulation, fertilization and/or the implantation of the embryo in the uterus. Plan B contains a progestin. Mifepristone (RU486) can be used 7­9 weeks after unprotected sex. It competes with progesterone for the progesterone receptor so the softened uterine wall is no longer maintained and the embryo is expelled with the menstrual flow. Surgical abortion now.org naral.org Methods that Prevent Birth after Methods Unplanned Intercourse Unplanned Plan B fda.gov­­mifepristone plannedparenthood.org nrlc.org Roe v. Wade: Two Sides Gannett Health Services (Weblinks) Birth Control Pregnancy Disease (STI) Prevention Sexuality and Relationships Sexual Health Care Sexual Assault (or call me, since this is something I will not tolerate). Gannett Health Services ...
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This note was uploaded on 04/04/2009 for the course BIO G 110 taught by Professor Wayne,r. during the Spring '07 term at Cornell.

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