Biopsychology of Sex Behavior

1. Biopsychology of Sex Behavior Lecture 5: Endocrine System Nelson, Ch. 2

2. Endocrine System • Information is communicated by the release of chemical agents and their detection by receptor activation • Intracrine: chemical mediation of intracellular events • Autocrine: substances feed back to influence the same cells that secreted them • Paracrine: paracrine cells secrete chemicals that affect adjacent cells • Endocrine: endocrine cells secrete chemicals into the bloodstream where they may travel to distant target cells • Ectocrine: substances are released to the outside of an individual and induce a biological response in another animal • Endocrinology: scientific study of the endocrine glands and their associated hormones • Neurohormone is released into the blood by a neuron, rather than by a gland • Neuroendocrinology: scientific study of transduction of a neural signal into a hormonal signal; as well as interactions between nervous and endocrine systems • General features of the endocrine system: • Endocrine glands are ductless • Endocrine glands have a rich blood supply • Hormones, products of the endocrine glands, are secreted into the bloodstream • Hormones can travel in the blood to virtually every cell in the body, and can thus potentially interact with any cell that has appropriate receptors • Hormone receptors are specific binding sites, embedded in the cell membrane or located elsewhere in the cell, that interact w/ a particular hormone or class of hormones

4. Endocrine System • Some glands in the body have both endocrine & exocrine structures (e.g., pancreas) • Steroid hormones: lipid-soluble; precursor to all vertebrate steroid hormones is cholesterol; they form reversible bond w/ carrier proteins while circulating in the blood and can move easily through the cell’s phospholipid membrane • Peptide hormones: water-soluble proteins; stored in endocrine cells in vesicles and are released (via exocytosis) in response to a specific stimulus • Monoamine and certain lipid-based agents are also hormones • Hormone signal must be cleared from the blood; the most common method involves the uptake and degradation (metabolism) of hormones by the kidney or liver

5. Endocrine Glands

6. Hypothalamus & Pituitary Gland • Hypothalamus: collection of nuclei that receive neural input from limbic system and brain stem (major interface between nervous and endocrine systems) • this brain structure is involved in sex, feeding, drinking, control of body temperature, and other behaviors that are important for survival • Output is both neural (to other neurons) and neurohormonal (either into blood to ant. Pituitary or into systemic blood circulation (via post. pituitary) • Some neurons in hypothalamus secrete releasing and inhibiting factors into capillaries that go to ant. pituitary, where they control secretion of tropic hormones that are released into general circulation • Other neurons send axons down to post. pituitary; neural firing of these neurons in hypothalamus causes release of these hormones into circulation • Pituitary gland: located at the base of the skull in bony depression called sella tursica • Connected to the base of hypothalamus by a funnel shaped stalk called the infundibulum, or pituitary stalk • “Pituitary” is derived from Latin for “mucous,” because early anatomists thought it collected waste from brain and excreted it via nose • Mammalian pituitary , aka hypophysis, is really two distinct glands fused into one • Anterior pituitary: derived from tissue from roof of mouth that migrates up and joins posterior pituitary tissue from base of brain that migrates down • Posterior pituitary: neural origin in the base of the brain; oxytocin & vasopressin released by neural firing (from hypothalamic neurons), but enter blood circulation rather than other neurons

8. Anterior Pituitary • Neurohormones from hypothalamus reach the anterior pituitary via hypothalamic-hypophyseal portal system, a special closed blood circuit in which to capillary beds are connected by a vein that extends down infundibulum Axons from hypothalamic neurosecretory cells release certain factors into primary plexus (hypothalamic side) Factors reach secondary plexus (pituitary side) cause cells in the anterior pituitary to release tropic hormones into general circulation Portal system

9. Posterior pituitary • Axons from cells in the supraoptic & paraventricular nuclei of the hypothalamus extend down infundibulum and terminate in posterior pituitary • In response to neural impulse, oxytocin and vasopressin are released from terminals in posterior pituitary and enter the bloodstream • In contrast to two-step process in the anterior pituitary gland, hormones can be released from posterior pituitary gland as fast as a neural impulse is conducted

11. Protein & peptide hormones • Most vertebrate hormones are proteins • Protein hormones: made up of individual amino acid building blocks • Peptide hormones: made up of a few amino acids in length (smaller than protein hormones) • Hypothalamic hormones: • Peptidergic neurons of the hypothalamic median eminence secrete a number of releasing hormones & inhibiting hormones (small peptides). These hormones act on cells in anterior pituitary (e.g., gonadotropin-releasing hormone, GnRH) • Note: dopamine (DA), which is a monoamine, also serves as a neurohormone in the hypothalamus to inhibit the release of prolactin from the anterior pituitary (aka prolactin inhibitory hormone, PIH)

12. Protein & peptide hormones • Anterior pituitary hormones: luteinizing hormone (LH), follicle-stimulating hormone (FSH), & prolactin • LH & FSH are secreted by cells called basophils • LH & FSH are known collectively as glycoproteins, and gonadotropins because, in response to GnRH, they stimulate steroidogenesis in the gonads as well as the development and maturation of gametes • Prolactin: promotes lactation in female mammals; stimulates formation and maintenance of corpus luteum in the ovaries of rats and mice • Posterior pituitary hormones: oxytocin & vasopressin, which are two closely related peptides • Oxytocin: profoundly influences reproductive function in mammals—important during birth, causing uterine contractions when uterus is responsive to it. Suckling reflex: oxytocin is released into the blood in response to sensory stimulation from the nipple • Gonadal peptide hormones: Müllerian inhibiting hormone (MIH), inhibin, activin, & relaxin • MIH: inhibits development of the Müllerian duct system into internal female sex organs • Inhibin: secreted by sertoli cells & granulosa cell; feeds back to block secretion of FSH from anterior pituitary; inhibin also inhibits the enzyme aromatase • Activin: in both testes & ovaries; stimulates FSH secretion

13. Steroid Hormones • Adrenal glands & the gonads are the most common sources of steroid hormones in vertebrates • Precursor to all vertebrate steroid hormones is cholesterol • Steroid hormones are lipid-soluble and move easily through cell membranes; they are not very soluble in water and must bind to water-soluble carrier proteins that transport them through the blood to their target tissues • In response to various protein hormones from the anterior pituitary, cholesterol is converted into steroid hormones in the adrenals and gonads • Pregnenolone is a progestin, and it is the obligatory precursor to all other steroid hormones. • Cholesterol  pregnenolone  steroid hormone • Testes: pregnenolone  androgens (e.g., testosterone) • Androgens are the obligatory precursors to all estrogens • Ovaries: Androgens  estrogens

15. Estrogen production

16. Gonads • Gonads have 2 functions: produce gametes (sperm or eggs) • Hormones produced by the gonads (primarily steroid hormones) are required for gamete development and development of the secondary sex characters • Gonadal hormones also mediate behaviors that bring sperm and eggs together • Functions of the gonads are regulated by tropic hormones from the anterior pituitary, known as gonadotropins • Testes: bilateral glands, located in most mammals in an external sac called the scrotum (and in most other vertebrates in the abdomen) • Seminiferous tubules contain both Sertoli cells & leydig cells • Sertoli cells nourish developing sperm and secrete inhibin, which inhibits the secretion of one of the gonadotropins (FSH) from anterior pituitary • Leydig cells produce steroid hormones, primarily androgens, which in turn provide negative feedback to hypothalamus and anterior pituitary; Leydig cells produce steroid hormones under the influence of gonadotropins from anterior pituitary

17. Testes

18. Hormonal interactions: hypothalamic-pituitary-testicular system

19. Seminiferous Tubules Green - Spermtagonia near surface of tubule,.Orange -Primary spermatocyte with granular nucleus.Black - Sertoli cell with a triangular shaped nucleus.Blue - Secondary spermatocyte near lumen.Purple - Spermatozoa - elongated small nucleus.Note - Spermatogenesis proceeds from the surface of the tubule to the lumen. Cells of Leydig stain pink and are oval cells with an oval nucleus. Myloid cells are smooth muscle cells with an elongated nucleus in a spindle shaped cell

20. Ovaries • Ovaries : In mammals, ovaries are bilateral structures located in the dorsal part of abdominal cavity, normally between the kidneys • Ovaries produce both gametes and hormones • Active ovaries exhibit cyclic changes in both functions, whereas testes are tonic, or constant, in their sperm-making and secretory activities during the breeding season • Ovary has functional subunits: • Follicles: 2 human ovaries contain ½ million immature follicles, of which only about 400 are ovulated; the rest degenerate (atresia) • Primary follicle: oocyte surrounded by a layer of granulosa (epithelial) cells. Surrounding follicle are thecal cells that secrete estrogens • Secondary follicle: ovum surrounded by zona pellucidum; granulosa cells proliferate, space (antrum) filled with follicle fluid between ovum & granulosa cells • Tertiary follicle: antrum enlarges; fluid rich in steroids • Graafian follicle: just before ovulation • Corpus Luteum (yellow body): after ovulation granulosa and thecal cells undergo rapid mitosis and are heavily vascularized  progestins • Corpus albacans (white body): corpus luteum degenerates and leaves scar, which does not produce hormones • Stroma: connective tissue and granulosa (interstitial) cells (similar to leydig cells)

21. Ovary

22. A 28-day menstrual cycle

23. Menstrual Cycle • Follicular phase: theca interna develops receptors for an anterior pituitary hormone called luteinizing hormone (LH)  produces androgens from cholesterol in response to LH • Granulosa cells develop receptors for follicle-stimulating hormone (FSH), and in response to FSH from anterior pituitary, convert androgens into estrogens • In response to FSH & estrogen, granulosa cells develop LH receptors  causes granulosa cells to produce progesterone at time of ovulation • Hypothalamus produces LHRH (luteinizing hormone releasing hormone, aka gonadotropin releasing hormone, GnRH) • GnRH is carried to anterior pituitary via portal system: causes anterior pituitary to release FSH and some LH into bloodstream • FSH stimulates ovary follicle to secrete estrogen (E) into blood • Thecal cells secrete androgens, under influence of LH • Granulosa cells aromatize the androgens to estrogens, under influence of FSH

24. Menstrual Cycle (cont.) • Estrogen exerts negative feedback on hypothalamus, decreasing GnRH (from hypothalamus) & FSH (from anterior pituitary). So far, this is similar process in male • BUT, by this time the follicle has grown so large, and needs so little FSH to stimulate it, that it secretes more and more estrogen • Eventually, a high enough level of estrogen occurs to trigger positive feedback loop at hypothalamus, resulting in outpouring of both FSH and LH into the blood • LH causes the ovum to rupture out of the follicle; the granulosa cells in the remnant of the follicle (corpus luteum) secrete progesterone • The ovum is swept into the fallopian tube by action of cilia, there it may or may not be fertilized • Also, progesterone increases vascular lining of uterus: preparation for implantation of embryo • Progesterone also exerts negative feedback on hypothalamus, which results in less LH and FSH; since LH is needed to trigger progesterone release, & since LH is declining, progesterone levels also decline (if pregnancy ensues, the placenta itself produces gonadotropin and eventually progesterone) • Since uterine lining depends on porgesterone for its heavy vascularization, it now breaks down and is eliminated as menstrual flow (in primates) or reabsorbed (in most other mammals • Note: only difference in the pattern of endocrine control between males and females is the positive feedback response to estrogen by females, resulting in outpouring of LH and FSH when estrogen levels are high enough

25. Hormonal basis of the menstrual cycle

26. Hormonal loops controlling menstrual cycle

27. Hormonal loops controlling menstrual cycle

28. Mechanisms of Hormone Action • Hormonal messages, or signals, evoke intracellular responses via signal transduction: chemical hormonal “message” is transformed into intracellular events that ultimately affect cell function • Signal transduction: sequence of events from time a hormone binds to its receptors to the ultimate response in a target cell • Hormone receptor types: • Steroid receptors: located inside cells, either in cytosol or in the nucleus; lipid-soluble, so they can penetrate the cell membrane to bind with these intracellular receptors. When receptors bind a specific steroid (or thyroid) hormone, they migrate to nucleus  gene transcription (& translation) • Protein & peptide receptors: found embedded in the cell membrane; hormone binds to extracellular domain. Some receptors in this category can have intrinsic enzymatic activity  directly activate intracellular proteins. Other receptors are coupled to enzymes (e.g., G proteins), which activate other (effector) enzymes  intracellular effects (including gene transcription)

29. Steroid receptors • Some hormones (e.g., steroid hormones) cross through the cell’s phospholipid membrane, and bind to the appropriate receptor; the hormone-receptor complex translocates to the nucleus and affects gene expression (genomic effects). In some cases, steroid hormones bind to receptors on the cell surface (nongenomic effects)

30. Protein & peptide receptors • Other hormones (e.g., peptide hormones) bind to receptors on the cell surface and this activates a signal transduction pathway; this can have an immediate effect on cellular function or the effects may take longer to occur (e.g., gene expression)

31. How hormones are regulated • Negative feedback: production of a product by target tissue feeds back to the source of the hormone & causes it to stop producing the hormone • Positive feedback: production of a product by the target tissue stimulates additional hormone production • Negative feedback is the most common type of regulatory mechanism in the endocrine system