Neuroendocrinology

1. Neuroendocrinology

2. Hormones Endocrine hormones Secreted directly into the blood Controlled by pituitary (master gland) and hypothalamus Exocrine Hormones Secreted into ducts Not controlled by pituitary gland or hypothalamus (e.g., gut hormones)

3. Hormones released from endocrine cells long latency, long duration of effect (mins/days) delivered via blood diffuse actions Neurotransmitters released from neurons short latency, short duration of effect (msec) released directly onto target cells specific actions This distinction has become blurred; e.g. peptide neurotransmitters/neuromodulators, monoamines, etc.

4. Anterior Pituitary (Adenohypophysis) Posterior Pituitary (Neurohypophysis) Pituitary Gland (Hypophysis)

7. Endocrine Hormones` Adenohypophysial hormones Direct Actions Somatotrophin (growth hormone; GH) Prolactin Melanocyte-stimulating hormone (MSH) Indirect actions Corticotrophin (ACTH) Thyrotrophin (TSH) Gonadotrophins Luteinizing Hormone (LH) Follicle-stimulating hormone (FSH) Neurohypophysial hormones Oxytocin Vasopressin

8. neural inputs Control of Adenohypophysial Hormones with Indirect Actions Hypothalamus Short Loop Releasing Factor Indirect Loop Adenohypophysis Trophic hormone Direct Loop Endocrine Gland Endocrine hormone Indirect Acting ACTH, TSH, LH, FSH Target tissues All loops are negative feedback loops. Increases in the amount of the substances monitored reduces further secretion of those substances.

9. neural inputs Control of Adenohypophysial Hormones withDirect Actions Hypothalamus Indirect Loop Inhibiting factor Releasing Factor Adenohypophysis Direct Loop Direct Acting Hormone Direct Acting GH, MSH, Prolactin Target tissues All loops are negative feedback loops. Increases in the amount of the substances monitored reduces further secretion of those substances.

11. Endocrine Hormones Adenohypophysial hormones Direct Actions Somatotrophin (growth hormone; GH) Growth hormone releasing hormone (GHRH)  somatotrophin (GH)  somatic tissues promotes growth by stimulating proteins synthesis of virtually all tissues GH release inhibited by somatostatin

12. Endocrine Hormones Adenohypophysial hormones Direct Actions Somatotrophin (growth hormone; GH) Prolactin Prolactin releasing factor prolactinmammaries stimulates milk production prolactin release inhibited by prolactin inhibiting factor (PIF) PIF secretion inhibited by stimulation of nipples

13. Endocrine Hormones Adenohypophysial hormones Direct Actions Somatotrophin (growth hormone; GH) Prolactin Melanocyte-stimulating hormone (MSH) MSH releasing factor  melanocyte-stimulating hormonemelanocytes stimulates melanin synthesis in melanocytes

14. neural inputs Control of Adrenocortical Hormones Hypothalamus Indirect Loop Short Loop CRF Adenohypophysis Corticotrophin (ACTH) Direct Loop Endocrine Gland Cortisol and Aldosterone Target tissues

15. Endocrine Hormones Adenohypophysial hormones Direct Actions Somatotrophin (growth hormone; GH) Prolactin Melanocyte-stimulating hormone (MSH) Indirect actions Corticotrophin (ACTH) regulates stress hormones and nutrient utilization (glucocorticoids) and water/mineral balance (mineralocorticoids)

16. Endocrine Hormones Adenohypophysial hormones Direct Actions Somatotrophin (growth hormone; GH) Prolactin Melanocyte-stimulating hormone (MSH) Indirect actions Corticotrophin (ACTH) Corticotrophin releasing factor (CRF) ===> corticotrophin ===> cortisol, aldosterone ===> tissues cortisol inhibits protein synthesis stimulates gluconeogenesis (synthesis of glucose from proteins) inhibits conversion of carbohydrates to fats principal stress hormone physiological stress—challenges to homeostasis psychological stress—perceived challenges limbic system participation aldosterone regulates electrolytes, especially sodium

17. Corticotrophin Controls secretions from adrenal cortex ad = on, renal = kidney, so adrenal = on the kidney

18. the adrenal gland is really two glands in one cortex = bark, medulla = core medulla is a modified sympathetic ganglion cortex is an endocrine gland Activity of both medulla and cortex are stress-related

19. What is stress?

20. What is stress? It is “a real or interpreted threat to the physiological or psychological integrity of an individual that results in physiological and/or behavioral responses. In biomedicine, stress often refers to situations in which adrenal glucocorticoids and catecholamines are elevated because of an experience.” McEwen, B. (2000) In G. Fink (Ed.) Encyclopedia of Stress, Vol. 3. San Diego: Academic Press.

21. What is stress? Is it a demanding stimulus or situation? “I’m under a lot of stress.” Is it a subjective experience? “I’m feeling stressed out.” depression Is it a physiological challenge? hunger, thirst, fatigue Is it an endocrine response? circulating stress hormones

22. Two types of stress • Systemic stress • physiological threat • 2. Processive stress • potential or eventual threat In adults, responses to processive, but not systemic, stress is blocked by lesions of the hippocampus Systemic stress is also referred to as physiological stress, and processive stress is oten referred to as psychological stress

23. Endocrine Hormones Adenohypophysial hormones Direct Actions Somatotrophin (growth hormone; GH) Prolactin Melanocyte-stimulating hormone (MSH) Indirect actions Corticotrophin (ACTH) Thyrotrophin (TSH) Thyrotrophin releasing factor (TRF or TRH)  thyrotrophin (TSH)  thyroid gland  thyroxine  tissues regulates development regulates metabolic rate in adulthood

24. neural inputs Control of Thyroid Hormones Hypothalamus Indirect Loop Short Loop TRF (TRH) Adenohypophysis TSH Direct Loop Thyroid Gland Thyroxine (T4) Target tissues

25. Thyroid Hormones as Regulators of Development Stimulation of Metamorphosis in Amphibians e.g. loss of gills, septation of lungs remodeling of gastrointestinal tract loss of tail, growth of limbs iin brain, thyroid hormones stimulate secondary neurogenesis of cerebellar Purkinje cells, development of optic tectum Thus, thyroxine stimulates both cell loss (apoptosis) and cell proliferation (mitosis) in different populations

26. Thyroid Hormones as Regulators of Development Thus, thyroxine stimulates both cell loss (apoptosis) and cell proliferation (mitosis) in different populations. This role contrasts with that of growth hormone. In the absence of growth hormone, tadpoles still undergo metamorphosis but have reduced size. In the absence of thyroxine, tadpoles continue to grow but fail to transform.

27. Analogous Effects are seen in mammals In mammals, growth hormone deficiency results in dwarfism; thyroid hormone deficiency results in cretinism. Dwarves reach developmental milestones at the normal time; they are simply of shorter stature. Hypothyroid individuals are also small, but more profoundly, developmental milestones are greatly delayed.

28. 15-20 years old, Congo-Kinshasa

30. Endocrine Hormones Adenohypophysial hormones Direct Actions Somatotrophin (growth hormone; GH) Prolactin Melanocyte-stimulating hormone (MSH) Indirect actions Corticotrophin (ACTH) Thyrotrophin (TSH) Gonadotrophins Gonadotrophin releasing hormone (GnRH) or Leuteinizing hormone releasing hormone (LHRH) luteinizing hormone (LH) and follicle stimulating hormone (FSH) gonads (ovaries or testes) estrogen and progesterone or androgens tissues organizational effects activational effects

31. Definitions of Sex Genetic (XX vs XY Gonadal (ovaries vs testes) Hormonal (cyclic vs constant release Morphological (clitoris, labia vs penis, scrotum) Behavioral (gender role behavior) Identity (what you consider yourself to be)

32. Control of Sex Hormones Hypothalamus neural inputs (GnRH) Adenohypophysis Luteinizing Hormone (LH) Follicle Stimulating Hormone (FSH) Testes (♂) Ovaries (♀) Testosterone (♂) Estrogen/Progesterone (♀) Target tissues

33. Sexual Dimorphisms Phenotypic differences between males and females They can be: anatomical physiological behavioral cognitive They can be: qualitative quantitative

34. Effects of Sex Hormones • Organizational Effects • structural • sensitive period • irreversible • masculinization/defeminization • Activational Effects • act on existing structure • no sensitive period • reversible

36. Bipotential tissues—those that can differentiate into tissues typical of either sex

37. Bipotential tissues: Undifferentiated tissue that can differentiate into either a male or female form. Sexual Dimophisms: Structures, functions or behaviors that differ qualitatively or quantitatively between the sexes.

38. Prototypical Experiment (Males) Castrate male hamster at birth (before period of brain differentiation) Test in adulthood inject with testosterone place with receptive female male typical behavior low mounting, intromission (ejaculation not possible) inject with estrogen and progesterone place with male female-typical behavior high darting, ear-wiggling, lordosis

39. Prototypical Experiment (Females) Neuter female hamster at birth and inject with testosterone (before period of brain differentiation) Test in adulthood inject with testosterone place with receptive female male typical behavior high (mounting) inject with estrogen and progesterone place with male female-typical behavior low (ear-wiggling, darting, lordosis)

40. Differentiation of the Brain Two processes both are dependent of fetal androgens Masculinization Induction of male characteristics paradoxically, dependent on estradiol Defeminization Suppression of female characteristics

41. cholesterol aromatase 5-alpha reductase estrodiol DHT

42. Why aren’t all females masculinized? α-fetoprotein binds to estradiol extracellulary and prevents entry into cell

44. ♂ ♁ medial preoptic area (MPOA) = “the” sexually dimorphic nucleus (SDN)

46. Sexual Differentiation Female is the “default sex;” no sex hormones are required for normal organization of the brain or peripheral tissues. Male development requires that testosterone be secreted from the fetal testes during a sensitive period of development. Masculinization and defeminization of the brain requires the conversion of testosterone to estradiol by neurons of the brain. Masculinization of peripheral tissues requires conversion of testosterone to dihydrotestosterone (DHT).

47. Sexual Dimorphisms Phenotypic differences between males and females They can be: anatomical physiological behavioral cognitive They can be: qualitative quantitiave

48. cholesterol aromatase 5-alpha reductase estrodiol DHT

49. XX Congenital Adrenal Hyperplasia (CAH)

50. XX Congenital Adrenal Hyperplasia (CAH)