1. Richard Raskind was a nationally ranked Men’s tennis player. In 1975, he had a sex change operation and became a nationally ranked woman’s player. She’s now a successful opthomologist

2. Sexual motivation differs from other motivational systems in two respects: (1)sexual dimorphism, and (2) biological function Examples of sexual dimorphism gender preference partner preference body size and mass brain symmetry spatial and visual abilities hormones Biological function Sex is not necessary for survival (despite what you might think) reproduction (and it’s therefore perfectly alright for the female of some species to eat the male after mating)

3. HORMONES AND REPRODUCTIVE PHYSIOLOGY Control Over Gonadal Function Cyclical Release of Gonadal Hormones Control Over Male Gonadal Hormones Other Hormones Mechanisms of Hormone Action

4. An Overview: HORMONES AND REPRODUCTIVE PHYSIOLOGY HORMONAL CONTROL OVER GONADAL FUNCTION Hypothalamus (synthesize Gonadotropin releasing hormone) GnRH Anterior pituitary (synthesizes gonadotropins) Lh+fsh Gonads - synthesize gonadal hormones estrogens androgens

5. Control Over the Release of GnRh Hormones and Reproductive Physiology Endogenous factors include control from SCN and hormonal input (estrogen and/or testosterone) Exogenous input includes olfactory bulbs, and other neural structures - which accounts for experiential control over GnRh release. Anterior Hypothalamic Preoptic Area Medial Basal Hypothalamus Suprachiasmatic nucleus Gonadotrophin Releasing Hormone is synthesized by parvocellular neurosecretory cells in AHPO and MBA. Rate of synthesis is under both endogenous and exogenous control

6. Hypothalamic Hypophyseal Portal System Gonadotrophs GnRH is released into the hypothalamic hypophyseal portal system, which is located in median eminance and provides a vascular link to the anterior pituitary. GnRh is released in anterior pituitary where it activates the synthesis of LH and FSH by Gonadotrophs - specialized hormone synthesizing cells. Control of LH and FSH synthesis by GnRh

7. The Menstrual Cycle: Control of Ovulation by LH and FSH The ovaries have two functions: (1) production of gametes (2) control of ovulation These occur cyclically. In humans the cycle is known as the menstrual cycle. It has a period of about 28 days. Phase 1 of cycle is proliferative phase. This is when follicles grow (clusters of cells surrounding the developing ova) The follicles secrete estrogen (estradiol and estrone), which inhibits release of LH. ovaries Developing ovarian follicle Pituitary FSH LH estrogen CYCLICAL RELEASE

8. The Menstrual Cycle: The olvulatory phase When the amount of estrogen released increases above some threshold, it causes a surge in the release of LH. (the pulse generating system is inhibited by estrogen and the surge system is activated) Pituitary FSH LH Pituitary FSH LH Mature graafian follicle This leads to the mature follicle rupturing and releasing the ova.

9. Pituitary FSH LH Corpus luteum progesterone The Menstrual Cycle The postovulatory phase The ruptured follicle becomes corpus luteum, and secretes both estrogens and progesterones.

10. Estrus Cycles These are receptivity cycles - estrus defines time of receptivity Animals with estrus cycles do not menstruate Reflex ovulators refer to animals in which ovulation is triggered by exogenous stimuli, such as sexual activity or the presence of odors. Environmental stimuli can also modify estrus cycles. Laboratory rodents that share the same air supply show synchrony in the occurrence of estrus. This is because of pheromones.

11. OTHER HORMONES ASSOCIATED WITH REPRODUCTIVE BEHAVIOR Prolactin - This is an anterior pituitary hormone synthesized from lactotrophs. Release is controlled by hypothalamically produced neuropeptides. Female - controls synthesis of milk Male - controls ejaculation Oxytocin - acts on smooth muscles Involved in ejaculation and climax Involved in labor and delivery Release of milk Pair bonding Vaspressin Intraspecific Aggression Pair bonding

12. HORMONAL CONTROL OVER MALE GONADAL FUNCTION The male gonads, the testes, have two functions: Production of testosterone and inhibin Production of sperm FSH controls the production of sperm (seminiferous tubules) FSH and LH control the production of testosterone from the interstitial cells. Release of FSH and LH is pulsed rather than cyclical

13. MECHANISMS OF HORMONAL ACTION At the systemic level of analysis, hormones act on reproductive physiology, development of secondary sexual characteristics, and on brain organization and function. Cellular mechanisms of hormone action A. Peptide hormones (prolactin, oxytocin, vasopressin, LH, GnRH) act by combining with receptor sites B. Steroid hormones 1. Gene expresssion 2. Rapid cellular response\ 3. Hormonal transformation 4. Gene memory

14. Steroid Hormones Act Through Gene Expression hormone Hormone receptor hormone Hormone receptor Gene products Synthesizes transcription factor mRNA

15. Hormonal transformation testosterone O 5-alpha-reductase 5 dihydroxytestosterone O Aromatase enzyme estrogen OH Aromatic ring

16. Fast Cellular Response Some cells have surface receptors that are activated by hormones. In such instances, the hormones serve as neurotransmitters and induce cellular depolarization..

17. Gene Memory Early in development the presence of particular hormones can produce a permanent change in the function of the cel nucleus. This constitutes an example of gene memory. The lordosis response of the female rat illustrates a shorter term example of gene memory. Lordosis is only triggered when animals have been primed by estrogen. For estrogen to be effective, the animal must have received estrogen earlier. This effect involves nuclear changes, because it doesn’t occur if animals are treated with protein synthesis inhibitors.

18. SUMMARY  The production of gonadal hormones is controlled by gonadotropins, LH and FSH, released from the anterior pituitary. Synthesis of LH and FHS is controlled by gonadtropin releasing factor (GnRH), which is synthesized in the hypothalamus.  The release of a surge of GnRH is controlled by secretory cells in the anterior preoptic area. The medial basal hypothalamus controls the tonic release GnRH controls the release of LH and FSH from the pituitary. LH and FSH control hormonal production in the gonads In the female, a surge of LH is responsible for ovulation.  Tonic release of LH in collaboration with FSH controls the synthesis of testosterone in the male.

19. .Hormone actions can result from hormonal transformation to other substances. Such transformations occur intracellularly and depend on the presence of particular enzymes.  In both sexes, GnRH secreteion is under negative feedback control from gonadal hormones.  Prolactin, oxytocin, and vasopressin are peptide hormones released from the anterior pituitary and are also involved in reproduction.  Steroid hormones can act by combining with receptors in the cell nucleus. This triggers the synthesis of transcription factors that affect subsequent gene expression  Both steroid and peptide hormones can produce a fast cellular response by activating extracellular receptors.  Hormonal effects in the nucleus can produce long-lasting changes in cellular function or responsiveness referred to as gene memory.

20. Organizational Role of Hormones Activational Effects of Hormones Hormones and Satiety

21. Organizational Role of Hormones Role of hormones during early development Early in development both genetic sexes have male and female urogenetical systems. Expression of the SRY (on Y chromosome)gene causes release of Mullerian inhibiting factor (MIH). MIH, if present, directs development of male urogenital system, and developing testes begin to secrete androgens. Organizational role of hormones

22. MASCULINIZATION AND DEFEMINIZATION Masculinization, by definition, is the process that results in a male-like hormonal response. Defeminization results when the female pattern of endocrine secretion is prevented. (One criteria is the presence of corpora lutea.) According to the organizational hypothesis, treatment early in development with high levels of androgens produces both masculinization and defeminization. Organizational role of hormones

23. Guinea pigs treated prenatally with testosterone develop male like genitalia (while retaining ovaries). These individuals with one kind of gonad but structural features characteristic of the opposite sex are called pseudohermaphrodites. Castration of either sex at birth doesn’t prevent elicitation of the lordosis response. This indicates that feminine pattern of behavior doesn’t require high levels of either androgens or estrogens. Organizational role of hormones

24. Masculinization also affects brain structure. The medial preoptic area is about 8 times larger in males than in females Sexually dimorophic medial preoptic area malefemale Organizational role of hormones

25. Comparison of effects of early estrogen and testosterone on female responsiveness TP= testosterone; EB = estrogen; N= normal; Cast = castrated; OV=ovariectomized Organizational role of hormones

26. Human Sexual Development Organizational role of hormones Genetic Factors - The presence of a functional Y chromosome is necessary for the development of male reproductive behavior. Female behavior can occur in people having a single functional X chromosome Chromosomal abnormalities can seriously impact sexual development. XO - (Turner’s syndrome) have only a single X chromosome. They develop as genetic females, but have markedly reduced sex drives.

27. Hormonal factors and human sexual development The person on the left is a genetic male, who in all other respects has the appearance of a female. The person on the right is a genetic female, who was raised as a male. Two examples of androgenital disorders.

28. Sexual dimorphism in the brain and human sexual behavior Humans have a sexually dimorphic nucleus in the preoptic area of the human brain. In males, the structure is larger and contains more cells. Differences in size do not emerge until around puberty, suggesting hormonal changes in later development can be critically important. LeVay looked at the size of hypothalamic structures in heterosexual and homosexual men. He found that a region known as INAH3 was significantly larger in heterosexual men than homosexual. This structure is also larger in heterosexual men then women.

29. Swaab and Hofman found that the vasopressin-containing subnucleus of the suprachiasmatic nucleus was larger in homosexual men then heterosexual men. Zhou et al. (1995) found that the central nucleus of the stria terminalis is 50% larger in heterosexual males than in females. In male-to-female transexuals, by contrast, the size is actually smaller than in heterosexual females. We need to be a bit sceptical about this data, and the implications, however, because of small sample size, and lack of essential controls.

30. Activational Effects of Hormones Effects on sexual behavior Hormones affect sexual behavior in two ways: they effect responsiveness and the effect motivation. Female rodents manifest sexual motivation by proceptive behavior.

31. Activational Effects of Hormones Primates In human reproductive behavior mating is not linked to the menstrual cycle. However, this kind of liberation should not be misinterpreted. Frank Beach (1974) put it this way: "No human female is 'constantly receptive.' (Any male who entertains this illusion must be a very old man with a short memory or a very young man due for bitter disappointment).” Pimates show emancipation, in terms of mating, but sexual motivation is still linked to estrous cycle. In monkeys mating decreases in frequency if home area is increased in size. Fluctuations in sexual desire vary cyclically.

32. Activaional effects of hormones Males Effects of hormones depend on experience. When hormone levels fall off, appetive aspect eventually ceases in rodents. Castration in humans does not always prevent sexual interest, although motivation is decreased, usually dramatically.

33. Phospholipase C alpha Progesterone receptors Activational Effects of Hormones: Mechanisms This illustrates how estrogen affects receptivity. 1. Estrogen activates receptor. 2. Receptor activates immediate early gene. 3. Progesterone receptors are synthesized. 4. Phospholipase C is synthesized and released in the central gray. Activaional effects of hormones

34. Males In rodents, sexual motivation depends on both experience and hormonal levels. Primates Sexual motivation weakens following castration. Testicular implants reinstate sexual motivation Activaional effects of hormones

35. Bulbocavernosis nucleus Normal male rat Castrated male rat Testosterone is necessary for maintenance of some aspects of brain structure. How a trophic mechanism is linked to sexual motivation Activaional effects of hormones

36. Hormones And Satiety of Sexual Behavior The Coolidge Effect - Male sexual behavior depends on partner novelty. Orgasm depends on spinal cord circuits, and can occur in patients with severed spinal cords. Apparently, orgasm involves two systems - one responsible for uterine contractions or ejactulation - the other is responsible for the cognitive component.

37. EEG correlates of orgasm Heath (1972) found that orgasms, which were induced by electrical or chemical stimulation of the brain, were accompanied by a spike and wave waveform (which is an epileptic pattern) in the nucleus accumbens septi. Oxytocin and satiety of sexual behavior. Release of oxytocin may play two roles: A peripheral role controlling smooth muscle contractions A central role controlling satiety

38. With the exception of primates, females are only sexually responsive during the estrus phase of the estrous cycle. Thus, high circulating levels of estrogens are a prerequisite for sexual motivation and receptivity. Early in development, the SRY gene on the Y chromosome triggers the synthesis of Mullerian inhibiting substance. This promotes the development of the male urogenital system. Human sexual motivation also depends on both genetic and hormonal factors. Partner preference and gender preference may both be linked to brain structure. According to the organizational hypothesis, levels of androgen early in development account for both masculinization and defeminization.

39.  The release of oxytocin may contribute to sexual satiety. Oxytocin, at lower levels, may also contribute to sexual motivation.  Female primates are also sensitive to hormonal influences and are more likely to initiate sexual contact during the ovulatory phase of the menstrual cycle.  Testosterone is necessary for the maintenance of sexual motivation in males of all species. Orgasm has both a cognitive and physiological component.

40. Consummatory Behavior Forebrain Copulatory System

42. System II: Forebrain copulatory control system Properties: 1. Structures are sexually dimorphic 2. Structures are linked, directly or indirectly, to the vomeronasal organ. 3. Structures contain high concentrations of hormone receptors.

43. Vomeronasal organ

44. Priming function of pheromones 1. Synchronization of ovulation - if female mice are placed in the same room, they cycle together. Similar findings have been obtained humans. 2. Induction of ovulation - some species, like the prairie vole, ovulate in response to chemicals in the urine of males. 3. Abortion of pregnancy - spontaneous abortion occurs when female mice are exposed to the odor of urine from strange males.

45. Signaling function of pheromones 1. Recognition of receptivity - dogs, rats, and elephants are examples of species in which odors from vaginal secretions indicate to males whether the females are receptive. 2. Recognition of mate - mice identify the odor of their mates and can distinguish urine of different mice. 3. Control over satiety - (The Coolidge effect)

46. Sex differences in vomeronasal organ In rats, the vomeronasal organ is 40% larger in males than it is in females. Two functions: inhibition of female behavior and activation of male behavior

47. Amgydala Approximate location, ventral forebrain lateral to internal capsule. 1. Olfactory amygdala 2. Medial amygdala (associated with VOM) 3. Basolateral amygdala 4. Cenral amygdala

48. Medial Preoptic Area (MPOA) In males, the MPOA is essential for mating. This includes the sexually dimorphic nucleus. The critical region is apparently not limited to the sexually dimorphic nucleus.

50. MPOA may not be essential for sexual motivation When tested on a conditioned place preference task, rats with lesions to MPOA preferred to go to place asssociate with female before, despite the fact they were unable to copulate. MPOA lesions inhibits female behavior in males. Thus, males with MPOA lesions are more likely to show lordosis. Prefers side associated with female Conditioning Test

52. Ventromedial Hypothalamic Nucleus This is also larger in males. In females, damage disrupts lordosis, but doesn’t effect sexual motivation.

53. Summary Copulatory behavior is controlled by brain stem and spinal cord circuits, and can occur in spinal animals. The brainstem circuitry is normally controlled by forebrain circuitry. In rodents, this circuitry is closely linked to the vomeronasal system and is sexually dimorphic. The medial amygaloid region is associated with the vomeronasal system. Damage to the medial nucleus of some species disrupts male sexual behavior. The medial preoptic area (MPOA) in males is essential for copulation. Damage to this region, however, does not abolish sexual motivation. The ventromedial hypothalamus of females is essential for lordosis.