HORMONES AND BEHAVIOR What animals do Mating Feeding Communicating Escaping predators Migration and dispersal BEHAVIOR HORMONES Biological signal molecules Secreted into blood Carried to target tissues Affect diverse processes Growth Development Physiology Behavior 1
HORMONES and BEHAVIOR Also known as behavioral endocrinology Integrative field Effects of hormones on behavior Effects of behavior on hormones Importance of mechanisms in evolution Regulation of life history variation HISTORICAL ROOTS Castration of domesticated animals for at least 2000 years Produces capons, steers, geldings, etc Removes primary source of testosterone Affects quality as food Affects behavior More manageable Less disruptive socially (less interested in sex, fighting) HISTORICAL ROOTS Castration of humans Castrati and Eunuchs: Prepubertal castration Castrati: Castration intended to retain singing voice Eunuchs: Castration intended to eliminate sex drive Employed as guards for women (including harems) Timing of castration important 2
BERTHOLD S EXPERIMENT 1849: A. A. Berthold performed first formal endocrinology experiment Demonstrated nonneural contribution by the testes required for normal development of a rooster 3
BERTHOLD S EXPERIMENT CONCLUSIONS Transplanted testes fully functional Birds with transplanted testes entirely normal Normal appearance Combs, wattles, plumage Normal behavior Normal vocalizing Normal aggression Normal mating BERTHOLD S EXPERIMENT CONCLUSIONS Hypothesized secretory product carried by blood to target tissues Learned later to be testosterone 4
HORMONES Organic molecules produced and released into blood by endocrine (ductless) glands and tissues Carried by blood to target tissues One or more examples produced by virtually all tissues HORMONES Generally play dual roles coordinating behavior and physiology Example: Same hormones regulate gamete maturation and mating behavior Mature gametes available when animals most actively engaging in reproductive behavior (Some exceptions) HORMONES vs NEUROTRANSMITTERS 5
HORMONE SPECIFICITY Specific hormones only affect certain cells Hormones affect different cells in different ways Target cells possess receptors for specific hormones Target cells vary in the transduction ti machinery they possess Diverse responses to particular hormones possible TINBERGEN S 4 QUESTIONS ABOUT BEHAVIOR How does it develop? What mechanisms cause it? How did it evolve? How does it contribute to survival? Niko Tinbergen LEVELS OF ANALYSIS PROXIMATE CAUSES Developmental mechanisms Genetic determinants of behavior Environmental determinants of behavior Environmental determinants of behavior Immediate causal mechanisms Systems for detection of environmental stimuli Systems for integrating and adjusting responsivenes to stimuli Systems for carrying out responses 6
LEVELS OF ANALYSIS ULTIMATE CAUSES Historical pathways leading to behavioral trait Evolutionary stages, from origin of trait to present Effects of selection on history of trait Effects of past and current usefulness on survival and reproductive success Both natural and sexual selection important HORMONE BEHAVIOR INTERACTIONS HORMONE BEHAVIOR INTERACTIONS Proximate Hormones affect development and expression of behavior Do not cause behavior themselves Do not cause behavior themselves Affect frequency and intensity of expression Organizational / activational effects 7
HORMONE BEHAVIOR INTERACTIONS Ultimate Mechanistic control of behavior affects fitness Mechanisms shared by related taxa Affects evolution of both behavior and mechanisms underlying development and expression of it 8
9
10
Overview of the Endocrine System I. The endocrine system: general considerations Definitions Classes of hormones Vertebrate endocrine glands II. Hypothalamus/pituitary Anatomy Anterior pituitary hormones Posterior pituitary hormones Hypothalamic releasing hormones III. Pineal gland Melatonin IV. Thyroid gland Thyroid hormone V. Adrenal gland Catecholamines Adrenal steroids VI. Gonads Male& Female Androgens Progesterone Estrogens VII. Digestive system Pancreas Stomach/small intestine VIII. Mechanisms of hormone action General considerations Hydrophilic hormones (Peptides/amines) Lipophilic Hormones (Steroid hormones/ thyroid hormones) 11
WHAT EXACTLY ARE HORMONES? Organic molecules produced and released into blood by endocrine (ductless) glands and tissues Carried by blood to target tissues Specific hormones only affect certain cells and hormones affect different cells in different ways Target cells possess receptors for specific hormones Target cells vary in the transduction machinery they possess Diverse responses to particular hormones possible Effects are typically slower and longer lasting than effects of the nervous system Various intercellular signaling strategies As opposed to: Nelson Fig. 2-1 THE NERVOUS SYSTEM AND THE ENDOCRINE SYSTEM ARE HIGHLY INTEGRATED! How do hormones influence the nervous system? Neurogenesis (new neurons) Apoptosis (death of neurons) Synaptogenesis (new synapses) Neuritogenesis (new inputs) Conduction velocity Alter membrane potential Thus, hormones can act as neuromodulators How does the nervous system influence endocrine system? Neurons secrete hormones ( neurohormones ) Neurons induce endocrine glands to secrete hormones Neurons alter target cell sensitivity 12
Classes of hormones 1.Steroid hormones: Derived from series of enzymatic modifications of cholesterol Androgens like testosterone, estrogens like estradiol, progestins like progesterone (androgens, estrogens, and progestins are sometimes referred to as sex steroid hormones ) Also, glucocorticoids like cortisol or corticosterone and mineralocorticoids like aldosterone, etc. 2. Fatty acid derivatives (prostaglandins) Classes of hormones, continued 3. Amino acid derivatives Thyroid hormone (coupling of two iodinated tyrosines) Amines: Epinephrine and Norepinephrine, Melatonin and Dopamine 4. Peptide hormones Size range: 3 amino acids (thyrotropin releasing hormone) to about 200 amino acids (e.g. prolactin, growth hormone) -produced by transcription of a hormone gene, translation of mrna, proteolytic processing and other enzymatic modifications to produce mature peptide hormone Major vertebrate endocrine glands Endocrine glands: Ductless Rich blood supply Secrete chemical messengers (hormones) into bloodstream Hormones affect only cells that have appropriate receptors Nelson Fig. 2-3 13
Two key components of endocrine system: The Hypothalamus and Pituitary Hypothalamus organized into nuclei -clusters of neuronal cell bodies Nelson 2-4 Intermediate pituitary Hormones of the posterior pituitary (both also produced in discrete brain regions) 1. Arginine vasopressin (AVP) Cys-Tyr-Phe-Gln-Asn-Cys-Pro-Arg-Gly-NH2 or Arginine vasotocin (AVT):nonmammals Cys-Tyr-Ile-Gln-Asn-Cys-Pro-Arg-Gly-NH2 Physiological roles: fluid balance and blood pressure Behavioral roles too (pair bonding) 2. Oxytocin or related peptides Physiological roles: Smooth muscle contraction mammary gland, uterus, male reproductive tracts Behavioral roles too (pair bonding) Cys-Tyr-Ile-Gln-Asn-Cys-Pro-Leu-Gly-NH2 Nelson 2-6 To general circulation (in median eminence) Hormones of the anterior pituitary (all peptide hormones) Gonadotropins: Luteinizing hormone (LH) Testosterone synthesis Induce ovulation Follicle stimulating hormone (FSH) Gamete maturation Estrogen synthesis Thyroid stimulating hormone (TSH) Thyroid gland growth Thyroid hormone synthesis All are glycoproteins and share a common alpha subunit but have different beta subunits that confer specificity To general circulation Nelson 2-6 14
Hormones of the anterior pituitary, continued: Pro-opiomelanocortin (POMC) gives rise to: Anterior pit. Intermediate pit. { { ACTH LPH ACTH LPH END MSH CLIP Simplified from Nelson 2-22 LPH Note: ACTH and endorphin produced in discrete brain regions as well 1. Adrenocorticotropic hormone (ACTH) END -Glucocorticoid synthesis by adrenal cortex -Behavioral effects too (learning/memory and food uptake) 2. LPH, CLIP:?? 3. Melanocyte stimulating hormone (MSH): coat, skin color (not in Humans) Endorphin ( END): Endogenous opioids, pain modulator Hormones of the anterior pituitary, continued: Growth hormone (GH) Somatic cell growth/ bone growth via insulin-like growth factor secretion Metabolic effects (glucose, amino acids) Prolactin (PRL) Lactation (mammals) Crop milk production (some birds) Nutritious secretions (some fish) Incubation patch edema (birds) Freshwater adaptation (migrating fish) Behavioral effects too Parental care in multiple vertebrate species Water drive (salamanders) Hypothalamic releasing or inhibiting hormones (All peptide hormones except dopamine-made directly from tyrosine) Gonadotropin releasing hormone (GnRH) -induces gonadotropin secretion (LH and FSH) Gonadotropin inhibiting hormone (GnIH) -the opposite (and other things) Thyrotropin releasing hormone (TRH) -induces TSH secretion Corticotropin releasing hormone (CRH) -induces ACTH secretion Somatostatin-inhibits GH secretion Growth hormone releasing hormone (GHRH) -induces GH secretion Prolactin inhibiting hormone (PIH): Most likely dopamine -inhibits PRL secretion 15
The pineal gland Secretes melatonin in absence of light Inhibits reproductive axis in seasonally breeding mammals Influences sleep/wake cycle (from tryptophan) Nelson 2-10 The thyroid gland TSH (from Anterior Pit.) Follicle 80% 20% Target tissues Nelson 2-7 The adrenal glands (Angiotensin II+) Aldosterone (ACTH+) OR OR Cortisol Corticosterone Sympathetic input Nelson 2-9 (ACTH+) AND Adrenal androgens Epinephrine Norepinephrine (from tyrosine) 16
Sex steroid biosynthesis in the gonads Pregnenolone Progesterone Androgens 5 reductase Dihydrotestosterone (DHT) Aromatase Estrogens 11- ketotestosterone (11-KT) (Important androgen in many fish) http://www.physci.ucla.edu/research/schlinger/kirandhea.html Nonaromatizable to estrogens Male gonads: testes FSH LH Peripheral tissues, brain Testosterone Nelson Fig. 2-11 Female gonad: ovaries LH FSH Testosterone FSH Estradiol LH Peripheral tissues, brain Nelson Fig. 2-12 Estradiol Progesterone 17
Other endocrine glands/tissues of note Parathyroid glands: Parathyroid hormone (calcium balance) Pancreas: Insulin (decrease blood glucose) Glucagon (increase blood glucose) Skin: Vitamin D (calcium balance) Stomach/Duodenum: Secretin (neutralize acid from stomach) Cholecystokinin (induce pancreatic enzymes, bile secretion) Gastrin (Stomach secretions) Multiple other peptides implicated nutrient digestion/absorption and in feeding behaviors White adipose tissue: Leptin (decrease feeding) Feedback loops often control hormone synthesis Nelson Fig. 2-36 HOW DO HORMONES WORK? Part I: Hydrophilic (Water soluble) Hormones use membrane receptors: Amines, peptide hormones Activate 2 nd messenger cascades Gets signal across membrane Amplifies hormonal signal Cross-regulation with other signals Can change cell function without new protein synthesis Cell shape, movement, ion channel activity, secretion, enzyme activity Can also change cell function via new protein synthesis 18
A very common membrane receptor type: G-protein coupled receptor Peptides Etc. Cell membrane Bockaert and Pin, 1999 G protein coupled receptors: camp as second messenger Adenylate cyclase subunit of G protein exchanges GDP for GTP, activates adenylate cyclase Also ion channels, transcription factors, etc. MODIFIED from Nelson 2-16 G protein coupled receptors: Calcium as second messenger Protein kinase C Phospholipase C is activated by GTP bound G protein subunit Substrate phosphorylation Additional kinase activation MODIFIED from Nelson 2-17 19
Diversity of effects from same hormone: AVP as an example V 2 R V 1a R V 1b R (or V3) AVP AVP Gs Gq Gq Activate Adenylate Activate Phospholipase Activate Phospholipase cyclase camp C IP3 and Ca2+ C IP3 and Ca2+ Water reabsorption in kidney Vascular smooth muscle contraction Behavioral effects (Pair bonding) Modulate ACTH release Part II: Lipophilic, or fat soluble, hormones (steroid hormones and thyroid hormones) primarily use intracellular receptors, also known as nuclear receptors GENERALLY slower acting, and have longer lasting effects than hydrophilic hormones i.e. Cortisol (a lipophilic steroid hormone)- chronic stress response leads to elevated blood glucose levels from increased gluconeogenesis, and increase blood amino acid levels from muscle and connective tissue protein breakdown (to combat starvation) Contrast with a hydrophilic hormone: Epinephrine (bioamine, works via G protein-coupled membrane receptor) -acute stress response leads to reinforcement of sympathetic output (elevated heart rate, blood pressure) as well as rapid elevation of blood glucose levels Intracellular (nuclear) receptor function No hormone Cytoplasm?? Ribosomes R R Nucleus Target gene 20
Intracellular (nuclear) receptor function e.g. Estradiol Cytoplasm?? 2 nd messengers etc. New protein Nucleus AAA New mrna Best known pathway R R Target gene Ligands (in order of potency) Receptor Specificity examples Nuclear receptor 17 estradiol=diethylstilbestrol (DES) >estrone DHT=11- ketotestosterone >testosterone>>dhea Progesterone Cortisol=corticosterone>>cortisone Aldosterone Triiodothyronine>Thyroxine Estrogen receptor (ER) Androgen receptor (AR) Progesterone receptor (PR) Glucocorticoid receptor (GR) Mineralocorticoid receptor (MR) Thyroid hormone receptor (TR) 21