Chp 8 HormoneBehavior Relations in the Regulation of

Chp 8: Hormone-Behavior Relations in the Regulation of Parental Behavior Overview: • Parental behavior evolved to supplement physiological mechanisms of reproduction--increasing the likelihood that the offspring will survive. • Different patterns of parental behavior • In females, hormones of pregnancy synchronize several events: – reproductive tract: stimulate uterine contractions (parturition or childbirth) – mammary gland: stimulate production and secretion of milk (lactation) – central nervous system: stimulate parental behavior • In males, hormonal changes are not strongly linked to parental responses • Consider two main examples in detail: – hormones, pregnancy and parental behavior in the female rat – hormones and parental behavior in male and female ring doves • Link: oxytocin--maternal behavior--social bonds

Hormonal Regulation of Parental Behavior Parental behavior varies in different species: Species exhibiting oviparity (egg laying): • Ex: birds, reptiles, fish • parental behavior involves: – laying eggs (and building nests) – incubating eggs until they hatch – brooding--care of hatchlings by providing warmth, feeding and protection Species exhibiting viviparity (birth of live young): • Ex: rats, mice, horses, primates (humans) • parental behavior involves: – care of the young at the time of birth--warmth, feeding (nursing), protection

Hormonal Regulation of Parental Behavior Three main patterns of parental behavior based on developmental status of young: Nesting Pattern: • species with altricial newborn: young that are very immature at birth--cannot see, hear or move well, nor regulate their body temperature or feed themselves • require extended parental care (prolonged care in nests) • Avian species: robins, pigeons, doves – parental care involves building nests, feeding, warmth, protection (aggression toward intruders) – 80% of all bird species are altricial • Mammalian species: rats, rabbits, cats – parental care involves building nests, feeding (nursing), licking to stimulate waste elimination, pup retrieval, and protection

Hormonal Regulation of Parental Behavior Three main patterns of parental behavior based on developmental status of young: Leading-Following Pattern: • species with precocial newborn: young that are quite mature at birth--young have vision, hearing, locomotive ability, and the ability to achieve thermoregulation • parental care is limited--young depend on mother food (may include nursing) and protection, but soon after birth young can feed themselves • in many instances, the mother leads the young who follow her • Avian species: chickens and ducks (10% avian species) • Mammalian species: ungulates (sheep, cows), guinea pigs, whales

Hormonal Regulation of Parental Behavior Three main patterns of parental behavior based on developmental status of young: Clinging-Carrying Pattern: • species with semialtricial/semiprecocial newborn: young are considered “intermediate” in development compared to altricial and precocial species; typically, young can hear and see, but require assistance in locomotion • parental care involves transportation (young will cling to mother or be carried by her), feeding (nursing), thermoregulation and protection • Avian species: gulls and terns (10% avian species) – nestbuilding is minimal, young are fairly mobile and parents feed young special food which is often regurgitated • Mammalian species: most primate species (including humans)

Hormonal Regulation of Parental Behavior What role do hormones play in parental behavior? • female rat as a model Broad overview: • events that occur with mating, fertilization and the start of pregnancy • events that occur during pregnancy (22 gestation period in the rat) • events that occur at the end of pregnancy: – parturition – lactation – maternal behavior – aggressive behavior – postpartum estrus

Female Rat is a Spontaneous Ovulator: Gn. RH Neuron HYPO Ovulation: • as follicles develop in ovary + Gn. RH ANT PIT FSH LH LH surge Gn. RH surge – increasing levels of estrogen are released – in female rats, increases in estrogen lead to a Gn. RH surge (positive feedback) follicle estrogen OVARY – Gn. RH surge leads to LH surge – LH surge leads to ovulation “ovulation” Gn. RH: gonadotropin-releasing hormone FSH: follicle stimulating hormone LH: luteinizing hormone

Formation of the Corpus Luteum Not Spontaneously Functional: • corpus luteum will not form unless female engages in copulation – Ex: rats • • • critical stimulus--vaginocervical stimulation (e. g. , intromissions) insertion of penis into vagina by male during mating will stimulate a neuroendocrine reflex in the female leading to release of PRL which then acts to form the corpus luteum will secrete progesterone PRL Neuroendocrine Reflex PRF Neuron HYPO + PRF ANT PIT PRL spinal cord follicle egg OVARY “corpus luteum” forms PRF: prolactin releasing factor PRL: prolactin vaginocervical stimulation progesterone

Female Rat as a Model Events that occur with mating, fertilization and the start of pregnancy: • a female rat has gone through a spontaneous estrous cycle – increased estrogen lead to a Gn. RH surge, LH surge and ovulation – increased estrogen followed by a preovulatory rise in progesterone stimulated proceptive and receptive behaviors--female mated with a male rat (multiple eggs are released and fertilized by sperm leading to development of several embryos) • intromissions associated with mating activated a neuroendocrine reflex leading to formation of the corpus luteum – prolactin maintains the corpus luteum – LH stimulates production of progesterone from corpus luteum (smaller amounts of estrogen) – estrogen: important for preparing uterus for implantation – progesterone: important for implantation of embryo into uterine wall and maintenance of pregnancy

Female Rat as a Model Events that occur with mating, fertilization and the start of pregnancy: • a placenta will be formed between each developing embryo and will become embedded into wall of uterus • placenta is a high vascularized organ that allows nutritive substances and gases in mother’s blood to diffuse to MOM embryo nutrients gases embryo and a mechanism for metabolic waste products metabolic wastes to leave developing embryo • placenta can also produce hormones placenta

Female Rat as a Model Events that occur during pregnancy: • pregnancy lasts approximately 22 days in the rat (gestational period) • progesterone: levels rise shortly after mating and are elevated throughout pregnancy until near parturition (end of pregnancy) • estrogen: levels are relatively low during first half of pregnancy, but rise significantly during the second half of pregnancy • midway through pregnancy (days 12 -13), regulation of ovarian hormone secretion switches from Mom’s anterior pituitary to the placenta – LH (released from Mom’s pituitary) is replaced by chorionic gonadotropin – PRL (released from Mom’s pituitary) is replaced by placental lactogen – species differences in terms of when, and if, this switch takes place (summarized in Table 8. 1)

Female Rat as a Model 1 1 st Half 12 2 nd Half 22 Placenta OVARY LH Mom’s Anterior pituitary PRL follicle egg “corpus luteum” progesterone (estrogen) chorionic gonadotropin placental lactogen gonadal steroids

Female Rat as a Model Events that occur during pregnancy: • mammary glands must develop to provide milk for nursing (lactation) • full development of the mammary glands requires hormones and stimulation of the nipples and genital region • hormonal control: – progesterone stimulates proliferation of secretory cells located in the alveoli of mammary gland – estrogen stimulates duct development (carry milk from secretory cells to nipple) – prolactin (placental lactogen) stimulates synthesis of milk by secretory cells – at parturition, with nursing of young, oxytocin (from Mom’s posterior pituitary) will stimulate release of milk (milk-letdown) – at parturition, with nursing of young, prolactin (from Mom’s anterior pituitary) will rise and stimulate milk synthesis

Female Rat as a Model Events that occur during pregnancy: • somatosensory control: – during pregnancy, the female rat will lick her ventral body region (nipples and genital region) – this sensory input is critical for normal development of mammary glands – Exp. #1: if you block the ability of a female to lick her ventral region by fitting her with a collar so that she can’t lick her body, mammary development will be significantly impaired (50% of normal development on day 21) – Exp. #2: if you take another group of collared females (that cannot lick themselves), and stimulate them with a brush along the nipples and genital region, you can stimulate full mammary development

Female Rat as a Model Events that occur at the end of pregnancy: • levels of progesterone drop • levels of estrogen remain elevated • levels of prolactin rise • These hormonal events (and others) signal the end of pregnancy, initiate labor (parturition), and initiate maternal behavior and maternal aggression. • In addition, the process of giving birth--uterine-cervical-vaginal stimulation-stimulates postpartum estrus: • 8 -11 hours after parturition, females will be sexually receptive and will mate • 18 hours after parturition, ovulation occurs and the female can become pregnant (although implantation is delayed while female engages in nursing)

Female Rat as a Model Maternal Behavior: • 4 components of maternal behavior in the female rat: – nestbuilding – pup licking – nursing – pup retrieval • maternal behavior increases gradually during 2 nd half of pregnancy--all components of behavior can be seen 24 -48 hours prior to parturition • maternal behavior lasts for 3 -4 weeks

Female Rat as a Model Maternal Aggression: • aggression displayed toward other adults viewed as “ intruders” – When an intruder comes near the nest, the mother will approach and sniff the intruder and then launch an attack that is aimed at the intruder’s neck and head region. The female bites at the neck of the intruder, climbs its back and pins it in place. The intruder usually will flee, but if escape is not possible, the intruder will become immobile and may turn over on its back--freezing and submissive behavior usually terminates the female’s aggression, although repeated attacks can occur. • aggressive behavior protects newborn from attacks and cannibalism • increases gradually during 2 nd half of pregnancy--high levels of aggression seen 2448 hours prior to parturition • maternal aggression also lasts for 3 -4 weeks

Female Rat as a Model Hormones have two main effects on processes associated with pregnancy: • hormonal “priming”--action of one or several hormones that prepare the way for subsequent hormones to produce their effects – elevations in estrogen and progesterone during pregnancy set the stage for elevated levels of estrogen to stimulate several events at parturition • hormonal “triggering”--action of estrogen in triggering or stimulating several events at the time of parturition – estrogen levels are elevated while progesterone levels drop – estrogen acts to stimulate: maternal behavior, aggressive behavior, sex behavior, uterine contractions and lactation – estrogen’s actions involve several processes: 1) increased expression of the estrogen receptor, 2) increased expression of receptors for other hormones, 3) increased synthesis and release of other hormones

Female Rat as a Model hormonal “priming” • elevations in estrogen and progesterone during pregnancy stimulate the expression of estrogen receptors within MPOA (but not within hypothalamus!) – estrogen receptors within the MPOA reach “peak” levels by day 13 of pregnancy and remain elevated through day 22 (parturition) – replicate finding--pretreatment of nonpregnancy females with estrogen and progesterone for 16 days can elevate estrogens receptors within MPOA • the “priming” effect of estrogen and progesterone on estrogen receptors within MPOA is thought to be important for the rapid onset of maternal behavior – MPOA is important for maternal behavior--lesioning MPOA will block maternal responses – estrogen implants in MPOA (in addition to elevated levels of progesterone) can stimulate maternal behavior in nonpregnance female rats

Female Rat as a Model hormonal “triggering” • estrogen levels are elevated while progesterone levels drop • drop in progesterone allows estrogen to stimulate several processes: – maternal behavior – sex behavior – uterine contractions – lactation • estrogen’s actions involve several processes: – increased expression of the estrogen receptor (ER) – estrogen--ERs-->increased expression of receptors for other hormones: oxytocin receptors, prostaglandin receptors, prolactin receptors – estrogen--ERs-->increased synthesis and release of other hormones: oxytocin, prolactin

Female Rat as a Model hormonal “triggering” myometrium of uterus pregnancy parturition progesterone inhibits uterine contractility drop in progesterone stimulates uterine contractility delivery of fetus

Female Rat as a Model hormonal “triggering” myometrium of uterus drop in progesterone oxytocin stimulates uterine contractility (posterior pituitary) prostaglandins stimulates uterine contractility (uterus) estrogen increases ERs in uterus; estrogen-ERs leads to: increase in oxytocin receptors in uterus increase in prostaglandin receptors in uterus

Female Rat as a Model hormonal “triggering” lactation pregnancy parturition progesterone inhibits release of prolactin & oxytocin into bloodstream increased release of prolactin & oxytocin nursing

hormonal “triggering” drop in progesterone HYPOTHALAMUS estrogen increases in ERs in neurons in hypothalamus; estrogen-ERs leads to: stimulates release of prolactin from anterior pituitary and oxytocin from posterior pituitary prolactin acts to stimulate milk synthesis while oxytocin acts to stimulate milk letdown (release) PRF Neuron PITUITARY Anterior PRF Posterior PRL MAMMARY GLAND Oxytocin Neuron oxytocin

Female Rat as a Model hormonal “triggering” female sex behavior pregnancy parturition progesterone inhibits display of female sex behavior (inhibitory part of the biphasic action of progesterone--due to prolonged exposure) display of postpartum estrus continuation of reproductive activities

Female Rat as a Model hormonal “triggering” female sex behavior drop in progesterone increase in ERs in VMH estrogen-ERs leads to: display of proceptive and receptive behaviors if a male is present

Female Rat as a Model hormonal “triggering” maternal behavior pregnancy parturition maternal behavior develops gradually during gestation, and is present 24 -48 hrs prior to parturition; high levels of progesterone inhibit rapid display of maternal behavior just prior to, and immediately after, parturition female shows maternal behavior (rapid onset) survival of offspring

hormonal “triggering” drop in progesterone estrogen increases ERs in neurons in MPOA & hypothalamus; estrogen-ERs leads to: + HYPO increased release of PRL into blood and brain, increased expression of PRL-Rs in MPOA, and maternal behavior E MPOA PRF Neuron E PITUITARY Anterior prolactin acts at PRL-Rs in MPOA to stimulate maternal behavior synergism between estrogen & PRL--1) PRL can stimulate ERs in MPOA, and 2) estrogen can increase PRL-Rs and PRL release in MPOA Maternal Behavior Oxytocin Neuron E PRF Posterior PRL MAMMARY GLAND ? oxytocin

Female Rat as a Model 2 phases to maternal behavior: • hormonal phase: – decrease in progesterone, increase in prolactin with elevated levels of estrogen – hormonal changes are important for the initiation of maternal behavior – however, once maternal behavior has been initiated, removal of the ovaries, adrenal gland, pituitary and placenta will not affect behavior (i. e. , removal of gonadal steroids and peptide/protein hormones present within bloodstream) • nonhormonal phase: – a transition occurs in which maintenance of maternal behavior depends on stimuli received from young (pups): suckling by pups at nipple, visual stimuli, auditory stimuli (crying) – neurocircuits within the brain that process somatosensory, visual, auditory information can feed into, and stimulate, neurons within MPOA to stimulate maternal behavior • transition period last approximately one week following parturition

OLD SLIDE: hormonal “triggering” drop in progesterone estrogen increases ERs in neurons in MPOA & hypothalamus; estrogen-ERs leads to: + HYPO increased release of PRL into blood and brain, increased expression of PRL-Rs in MPOA, and maternal behavior E MPOA PRF Neuron E PITUITARY Anterior prolactin acts at PRL-Rs in MPOA to stimulate maternal behavior synergism between estrogen & PRL--1) PRL can stimulate ERs in MPOA, and 2) estrogen can increase PRL-Rs and PRL release in MPOA Maternal Behavior Oxytocin Neuron E PRF Posterior PRL MAMMARY GLAND ? oxytocin

NEW SLIDE: hormonal “triggering” drop in progesterone estrogen increases ERs in neurons in MPOA & hypothalamus; estrogen-ERs leads to: increased synthesis and release of PRL into blood and brain, and stimulation of maternal behavior prolactin acts at PRL-Rs in MPOA to stimulate maternal behavior (rapid onset) synergism between estrogen & PRL 1) PRL may enhance interaction of estrogen to its receptor, 2) estrogen can increase PRL synthesis and release E MPOA + ? Maternal Behavior E HYPO PRL Neuron PRF Neuron E PITUITARY Anterior E PRF Posterior PRL MAMMARY GLAND Oxytocin Neuron oxytocin

Interaction Between Estrogen and Prolactin Estrogen and prolactin both act to facilitate maternal behavior at the level of the MPOA. How does this occur? • Prolactin can enhance interaction of estrogen with its receptor – Ex. Mammary gland – prolactin changes the form of the estrogen receptor within cytoplasm – 4 S receptor is found in the unstimulated tissue, while 8 S receptor is observed following administration of hormone; 8 S form shows increased binding of estrogen – prolactin changes the form of the estrogen receptor: 4 S-->8 S (in cytoplasm); thus, prolactin increases “sensitivity of ERs to estrogen” by changing the form of the receptor (can be thought of as increasing the number of “functional” ERs) – estrogen then binds to ER and stimulates its translocation from the cytoplasm to the nucleus; estrogen bound to ER in the nucleus can then mediate gene transcription • It is possible that prolactin is stimulating a similar process in MPOA to enhance display of maternal behavior--however, we don’t have direct proof!

Interaction Between Estrogen and Prolactin can act at the MPOA to stimulate rapid onset of maternal behavior. – In steroid primed females, administration of prolactin into the MPOA can stimulate rapid onset of maternal behavior. – Prolactin neurons exist within the brain and project into the MPOA (as well as within other brain regions). – A subset of prolactin neurons within the brain also accumulate estrogen receptors; estrogen can positively regulate levels of prolactin within the brain. . – There is also evidence that prolactin can be transported from blood into the brain via specific transporters. – If you block the rise in prolactin with an inhibitor bromocriptine, you can delay but not prevent the onset of maternal behavior. – Prolactin is believed to act by stimulating rapid onset of maternal behavior--critical because in real life, if mom (or dad) does not care for the pups they will die.

Interaction Between Estrogen and Prolactin Estrogen and prolactin both act to facilitate maternal behavior at the level of the MPOA. How do these mechanisms interact? Don’t fully understand. . . • Prolactin increases can increase sensitivity of neurons to the effects of estrogen. • Estrogen is important for the initiation of maternal behavior. • However, once maternal behavior is initiated, estrogen levels are relatively low, and are not believed to be important for maintenance of maternal behavior. • Suckling by pups is one stimulus that has been shown to be important for maintenance of maternal behavior. • Suckling increases levels of prolactin within the blood and brain. • Prolactin is believed to be important for the rapid onset of maternal behavior (which is critical). • Blocking prolactin levels delays the onset of maternal behavior but it does not prevent it…possibility that other mechanisms may also exist to facilitate response.

Female Rat as a Model 2 phases to maternal behavior: • hormonal phase: – decrease in progesterone, increase in prolactin with elevated levels of estrogen – hormonal changes are important for the initiation of maternal behavior – however, once maternal behavior has been initiated, removal of the ovaries, adrenal gland, pituitary and placenta will not affect behavior (i. e. , removal of gonadal steroids and peptide/protein hormones present within bloodstream) • nonhormonal phase: – a transition occurs in which maintenance of maternal behavior depends on stimuli received from young (pups): suckling by pups at nipple, visual stimuli, auditory stimuli (crying) – neurocircuits within the brain that process somatosensory, visual, auditory information can feed into, and stimulate, neurons within MPOA to stimulate maternal behavior • transition period last approximately one week following parturition

Female Rat as a Model Key differences between hormonal and nonhormonal phases on maternal behavior: • at parturition, the drop in progesterone allows the rise in estrogen to stimulate numerous processes including maternal behavior (stimulating the synthesis and release of hormones and the expression of their receptors) • once young are born, gonadal steroid levels are relatively low during nursing (even though female engages in maternal behavior) • stimuli from pups can maintain maternal behavior in the absence of high levels of estrogen – Ex. somatosensory stimuli associated with suckling at the nipple activates a neuroendocrine reflex leading to increased release of PRL and oxytocin within the bloodstream, and increased release of PRL within the MPOA

MPOA other stimuli ? Maternal Behavior HYPO other stimuli PRL Neuron PRF Neuron PITUITARY Anterior Oxytocin Neuron PRF Posterior PRL oxytocin suckling at nipple MAMMARY GLAND

Ring Dove as a Model Both male and female ring doves engage in parental behavior. • Parental behavior: – nest building, laying of eggs (by female), incubation of eggs, and brooding (care of hatchlings--warmth, protection, feeding) – feeding involves producing and regurgitating “crop milk” • Hormones play a major role in parental behavior in both sexes: – during courtship and nest building, the levels of estrogen and progesterone are high in female ring doves, and the level of testosterone is high in male ring doves – as levels of gonadal steroids drop following courtship and nest building, the female will lay eggs, and both the male and female ring doves initiate incubation behavior – rise in prolactin during incubation behavior is important for maintenance of incubation behavior and for initiation of brooding – somatosensory cues associated with incubating eggs stimulate prolactin synthesis and release within bloodstream and brain-->development of the crop gland, production of crop milk, and display of behaviros to care for young once hatched

Ring Dove as a Model During courtship and nest building: • gonadal steroids are high • gonadal steroids stimulate formation of a brood patch: – brood patch is a defeathered, highly vascularized and edemic (fluid-filled) area – this region will contact eggs during incubation, providing warmth to egg (important for development of embryo) – this region will also provide the parent with somatosensory stimulation important for maintaining release of PRL – a brood patch will be seen in male and female ring doves, as they both engage in incubation behavior • there are bird species in which neither the mother nor the father incubate eggs – Ex. brown-headed cowbird – considered parasitic as female lays her eggs in the nests of other birds – no brood patch is formed in either the mother or father brown-headed cowbird

Ring Dove as a Model Both male and female ring doves incubate eggs--incubation behavior. • incubation behavior is initiated as gonadal steroids decline and after eggs are layed • prolactin levels rise midway during incubation: – maintain incubation behavior – prepare Mom and Pop for the next stage--brooding: 1) development of crop gland, and 2) production of “crop milk” Both male and female ring doves show brooding behavior. • prolactin levels are high at initiation of brooding behavior – prolactin maintains crop gland production of “crop milk” – prolactin stimulates feeding the young --regurgitation of ”crop milk” – prolactin stimulates “sitting” on hatchlings to provide warmth

Ring Dove as a Model Initiation and maintenance of incubation behavior: remove eggs from nest drop in gonadal steroids, and laying of eggs decrease in prolactin levels (initiation) incubation behavior (sitting on eggs) “somatosensory stimulation” prolactin synthesis and release (maintenance) decrease in incubation behavior administer prolactin

Comparison--Female Rat and Ring Dove Interesting parallels between female rat and male and female ring doves: Female Rat Male & Female Ring Dove estrogen and progesterone prime the brain to respond to estrogen and PRL to initiate maternal behavior at parturition rise in gonadal steroids prime the brain to initially show incubation behavior after laying eggs shift in control of maternal behavior (nursing, pup retrieveal, licking) from gonadal steroids to stimuli associated with pups (e. g. , suckling at nipple) tactile stimulation from eggs is important for maintaining incubation behavior and for stimulating brooding responses PRL plays critical role