Chp 3: Hormonal Influences on Female Sex Behavior

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Chp 3 Hormonal Influences on Female Sex Behavior

• Female sex behavior can be divided into two
  components
• precopulatory behavior AKA proceptive
  behavior--the female approaches a male and shows
  solicitatious behavior to get the male to engage
  in copulation
• 3 components to proceptive behavior (female rat)
• approach
• orientation female presents anogenital region
  to male ear wiggling--rapid movement of head
  (serves to exicte male)
• runaway hopping and darting--hopping and
  rapid flight away from the male
• copulatory behavior display of lordosis (AKA
  receptive behavior)
• immobility
• arching of the back with an elevation in the rump
  head region can also include movement of tail
  laterally
• .

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Quantification of Proceptive and Receptive
Behaviors

• It may be important to determine the degree of
  proceptivity or receptivity of a given female,
  especially when looking at interactions between
  individuals.
• Ex. quantification of lordosis behavior
• strength of lordotic posture
• frequency of lordosis
• duration of lordosis
• lordosis quotient is calculated as a measure of a
  females receptivity
• lordotic postures by female/10 mounts by
  male X 100 LQ
• if a female shows 5 lordotic postures to 10
  mounts by male, then LQ50 this would be
  considered a moderately receptive female.

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Hormonal Influences on Female Sex Behavior

• Estrogen and progesterone play an important role
  in female sex behavior.
• Considering the female rat as a model
• estrogen
• enhance attractivity of the female to the male
  (increasing production of pheromones and
  vocalizations)
• induce a GnRH surge that will lead to an LH surge
  and subsequently ovulation
• estrogen and progesterone
• increase females willingness to approach a male
  and to show solicitious behavior
• these hormones will couple sex behavior with
  ovulation
• progesterone has biphasic effects on female sex
  behavior
• initially, increases in progesterone will
  stimulate female sex behavior
• prolonged exposure to progesterone will inhibit
  female sex behavior

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Hormonal Influences on Female Sex Behavior

• In many mammalian species, females show
  precopulatory and copulatory behaviors at
  specific times during their reproductive cycle.
• Definitions
• estrus refers to the day in which ovulation
  occurs
• behavioral estrus refers to the period of time
  during which female shows precopulatory and
  copulatory behaviors (AKA--behavioral heat)
• estrus cycle series of ovarian events that
  determines when an animal comes into estrus
• In females that ovulate spontaneously, the
  duration of an ovarian cycle can vary
• 4 days mice, rats and hamsters
• 16 days guinea pigs
• 28 days humans

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Ovarian Cycle

• There are 3 main phases of ovarian cycle
• follicular phase series of hormonal events
  GnRH--gtLH FSH--gtestrogen
• FSH stimulates primary follicles to enlarge and
  differentiate into inner granulosa cell layer and
  an outer thecal cell layer oocyte (egg) may also
  complete development
• LH and FSH act together to produce estrogen LH
  stimulates thecal cells to produce androgens, and
  androgens are converted to estrogens in granulosa
  cells via aromatase FSH increases aromatase
  activity in granulosa cells
• lasts 2-3 days in rodents and 10-14 days in
  humans
• periovulatory phase
• as follicle matures, rate of estrogen secretion
  increases
• in female rats, increase in estrogen will
  stimulate a GnRH surge followed by an LH
  surge--gtLH surge will cause the ovarian follicle
  to rupture--gtrelease the egg a rise in LH also
  induces a preovulatory surge of progesterone
  release from ovaries
• lasts about 12 hours in most rodents in humans
  it occurs over a period of 1-2 days

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Ovulation and GnRH Surge in Rats

• Ovulation
• as follicles develop in ovary
• increasing levels of estrogen are released
• in female rats, increases in estrogen lead to a
  GnRH surge (positive feedback)
• GnRH surge leads to LH surge
• LH surge leads to ovulation
• male rats are unable to show a GnRH surge in
  response to increases in estrogen

GnRH Neuron
HYPO

GnRH
ANT PIT
FSH LH
Estrogen
OVARY
GnRH gonadotropin-releasing hormone FSH
follicle stimulating hormone LH luteinizing
hormone
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Ovarian Cycle

• luteal phase
• once the follicle has ruptured and expelled its
  egg into Fallopian tube (oviduct), the remaining
  follicle may be transformed into the corpus
  luteum
• corpus luteum secretes progesterone which is
  important for 1) implantation of the egg into
  the uterine wall, and 2) maintenance of pregnancy
• in some species, corpus luteum is spontaneously
  functional, in other species, vaginal-cervical
  stimulation during copulation is required for
  formation of corpus luteum
• length varies depending on species in humans,
  lasts 10-12 days
• menstrual phase (species dependent)
• see uterine bleeding in species that have long
  ovarian cycles (primates)
• during luteal phase, estrogen and progesterone
  prepare uterus for implantation
• if the egg is not fertilized, then no embryo will
  implant into uterine wall, the corpus luteum will
  regress (die)
• drop in estrogen and progesterone levels will
  lead to sloughing off of the uterine wall
  (endometrium)--uterine bleeding

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Female Rat Estrous Cycle

• day 1--metestrus
• early ovarian hormone secretion is relatively
  low
• late start of follicular activity
• day 2--diestrus
• follicles continue to develop, see significant
  increases in estrogen levels
• day 3--proestrus
• early see further increases in estrogen
• late estrogen levels peak mid-late proestrus
  the rise in estrogen stimulates GnRH and LH
  surges the rise in LH will also stimulate
  preovulatory rise in progesterone
• day 4--estrus
• early ovulation (resulting from increases in
  estrogen and LH), and behavioral
  estrus--proceptive and receptive behaviors
  (resulting from increases in estrogen and
  progesterone)
• late declining levels of estrogen and
  progesterone
• depends on whether female engages in copulation

follicular phase
periovulatory phase
luteal phase
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Formation of the Corpus Luteum

• Spontaneously Functional
• following ovulation, the corpus luteum forms and
  secretes progesterone (and estrogen) for several
  days
• Ex humans
• Not Spontaneously Functional
• corpus luteum will not form unless female engages
  in copulation
• Ex rats
• critical stimulus--intromissions
• (insertion of penis into vagina by male) will
  stimulate a neuroendocrine reflex in the female
  leading to release of PRL which then acts to form
  the corpus luteum

PRL Neuroendocrine Reflex
PRF Neuron
HYPO

PRF
ANT PIT
PRL
spinal cord
follicle
egg
OVARY
vaginocervical stimulation
progesterone
corpus luteum forms
PRF prolactin releasing factor PRL prolactin
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Hormones and Female Sex Behavior

• How do gonadal steroids affect the nervous system
  to stimulate sex behavior?
• Female rat as a model
• both estrogen and progesterone are needed to
  stimulate female sex behavior--if you
  ovariectomize (OVX) a female rat, she will not
  show proceptive nor receptive behaviors
• if you OVX a female rat administer estrogen for
  1 to 2 days single injection of
  progesterone--gtsex behavior will occur 4 hours
  after the progesterone injection (activational
  effects of gonadal sterodis)
• rise in estrogen primes the brain to respond to
  progesterone
• rise in progesterone times the onset of
  behavioral estrus
• ventromedial nucleus of the hypothalamus (VMH)
  plays an important role in hormonal modulation of
  lordosis
• estrogen and progesterone act, in part, at the
  VMH to stimulate the display of lordosis in
  response to mounting by a male

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Ventromedial Nucleus of the Hypothalamus

• VMH is critical for hormone-mediated lordosis
  behavior
• bilateral lesions of VMH can reduce or eliminate
  lordosis
• estrogen and progesterone act at the VMH to
  activate female sex behavior
• if OVX an adult female rat, lordosis behavior
  will not be shown
• if you give estrogen for 2 days followed by a
  single injection of progesterone, lordosis
  behavior will be shown 4 hours later
• if you implant estrogen capsules within the VMH
  and administer progesterone systemically,
  lordosis behavior will be shown (estrogen acts
  specifically within VMH to stimulate lordosis
  this is also true for progesterone)
• mechanism (genomic)
• increases in estrogen lead to increases in ER
  within lateral VMH
• estrogen binds to ER induce expression of PR
  (genomic mechanism)
• rising progesterone levels then bind to PR induce
  the expression of other proteins that serve to
  activate lordosis (genomic mechanism)
• know that protein systhesis is critical to
  facilitation of lordosis--1) administration of a
  protein synthesis inhibitor inhibits lordosis,
  and 2) time-frame for effects to be seen takes
  3-4 hours
• neurons within VMH project to PAG changes in
  synthesis of proteins in VMH neurons leads to an
  increased state of excitability of neurons within
  the PAG that control motoneurons within brainstem
  and spinal cord

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Ventromedial Nucleus of the Hypothalamus

• What proteins are synthesized within the VMH that
  can lead to an increased state of excitability of
  neurons within the PAG?
• Recent evidence suggests
• evidence that estrogen and/or progesterone can
  increase the number of oxytocin receptors within
  VMH--gtadministration of oxytocin can stimulate
  female sex behavior (specific to VMH?)
• oxytocin may facilitate lordosis by altering
  other responses such as decreasing aggressive
  behavior or increasing pair-bonding
• evidence that estrogen can increase the number of
  acetylcholine receptors within VMH--gtadministratio
  n of acetylcholine within VMH can stimulate
  female sex behavior (this effect is also seen
  other brain areas)
• evidence that estrogen can also increase a 70,000
  MW protein--an isoform of phospholipase C that is
  transported to the midbrain periaqueductal gray
• How do these changes lead to increased
  excitability of PAG neurons?
• not presently known

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Periaqueductal Gray

• PAG--via input from VMH--is critical for
  hormone-mediated lordosis behavior
• lesions of the PAG can block display of lordossis
• PAG integrates hormonal and sensory inputs
• the PAG must receive excitatory input from VMH
  (critical)--gtincreased excitability of PAG
  neurons
• when a male mounts a female, somatosensory
  information will be relayed to the PAG to
  activate lordosis
• the PAG will excite neurons within the reticular
  formation of the brainstem (medulla)
• reticular formation integrates sensory and motor
  responses (within the spinal cord) for the
  display of lordosis--immobility, arching of head
  and rump and movement of tail laterally
• PAG also contains ERs, so estrogen may also act
  at the PAG to facilitate the display of lordosis

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Medial Preoptic Area

• Neurons within MPOA can have inhibitory and
  facilitatory effects on lordosis.
• Inhibitory
• estrogen-responsive neurons in MPOA project to
  the VMH and PAG
• neurons within the MPOA have inhibitory effects
  on lordosis
• lesion neurons within dorsolateral
  MPOA--gtfacilitation of lordosis
• stimulate neurons within dorsolateral
  MPOA--gtinhibition of lordosis
• estrogen can act to decrease electrophysiological
  activity of MPOA neurons
• current theory estrogen acts at VMH to increase
  excitatory drive on lordosis, while decreasing
  inhibitory tone by decreasing activity of
  neurons within MPOA
• Stimulatory
• GnRH neurons are also present throughout MPOA
  (located more medially)
• GnRH secretion into median eminence
  (neurohormone) will lead to follicular
  development, estrogen secretion, preovulatory
  rise in progesterone, LH surge and ovulation
• GnRH can also be secreted within brain
  (neurotransmitter) GnRH receptors are present
  within VMH and PAG, and administration of GnRH
  into VMH and/or PAG can facilitate lordosis

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Progesterone

• Progesterone has biphasic effects on sex behavior
  in the female rat
• progesterone interacts with PRs to stimulate the
  display of lordosis (as well as the display of
  proceptive behaviors)
• prolonged exposure to progesterone can inhibit
  sex behavior
• Mechanism of inhibitory effects
• progesterone can lead to a decrease in the number
  of PRs and ERs (considered a refractory state)
• It is essential that the elevations in estrogen
  and progesterone drop to low levels so that
  elevations in these two hormones can effect
  changes in protein synthesis within the brain to
  effect changes in behavior.

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Dopamine

• Dopamine is a neurotransmitter synthesized within
  two main cell groups
• substantia nigra
• dopaminergic neurons project to the basal ganglia
  to control general locomotion and execution of
  stereotyped movements
• ventral tegmental area
• dopaminergic neurons project to nucleus accumbens
  to control motivated behavior
• Background information
• estrogen can facilitate release of dopamine and
  hence dopamine-mediated processes
• further, it is known that dopamine is released
  within the basal ganglia and nucleus accumbens of
  female rats during sex behavior
• Thus, estrogen-enhanced release of dopamine
  within the basal ganglia and nucleus accumbens
  most likely acts to promote proceptive behaviors.
  Note dopaminergic activity is not believed to
  be important for the display of lordosis.

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Species Differences in Periovulatory Period

• In rats
• as follicles mature and grow in size, estrogen
  levels increase
• increase in estrogen leads to a GnRH surge, an LH
  surge, and the LH surge leads to ovulation
  (deterministic model)
• the rise in LH also stimulates secretion of
  progesterone from the ovary
• preovulatory rise in progesterone acts to couple
  behavioral estrus with ovulation (estrus)
• if mating occurs, the corpus luteum will form and
  secrete progesterone (luteal phase)
• In primates
• as follicles mature and grow in size, estrogen
  levels increase
• increase in estrogen leads to increased
  sensitivity of the pituitary to GnRH, the
  pituitary secretes more LH to a given amount of
  GnRH (LH surge), and the LH surge leads to
  ovulation (permissive model)
• there is no preovulatory rise in progesterone
• the corpus luteum will form spontaneously and
  secrete progesterone during the luteal phase

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Species-Specific Patterns--Sex Behavior
Ovulation

• spontaneous ovulation
• a series of hormonal events lead to the
  occurrence of ovulation
• Ex rats (hormonal events also time the
  occurrence of behavioral estrus)
• Ex humans
• induced ovulation
• behavioral estrus occurs in spontaneous cycles,
  but ovulation does not occur without copulation
• Ex rabbits, cats and ferrets
• induced estrus and ovulation
• both behavioral estrus and ovulation are induced
  by specific stimuli external to the female
• Ex prairie vole

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Induced Ovulation

• the ovaries produce waves of follicles, and
  follicles secrete estrogen
• increasing levels of estrogen stimulate
  behavioral estrus
• progesterone is not needed to stimulate sex
  behavior
• vaginocervical stimulation (via intromissions
  from male) will activate a neuroendocrine reflex
  resulting in GnRH release
• GnRH release will lead to LH surge and ovulation
• subsequent production of progesterone will
  maintain pregnancy if necessary

GnRH Neuroendocrine Reflex
GnRH Neuron
HYPO
GnRH
ANT PIT
stimulate sex behavior
LH FSH
LH
spinal cord
follicle
estrogen
OVARY
vaginocervical stimulation
ovulation
GnRH gonadotrophin releasing hormone FSH
follicle stimulating hormone LH luteinizing
hormone
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Induced Estrus Ovulation

• a female is reproductively inactive until exposed
  to a male
• a male pheromone stimulates GnRH release
  (neuroendocrine reflex)
• GnRH release stimulates FSH and LH release,
  follicular development and secretion of estrogen
• increasing levels of estrogen stimulate
  behavioral estrus
• vaginocervical stimulation (via intromissions
  from male) stimulates further GnRH release
• GnRH release will lead to LH surge and ovulation
• after ovulation, progesterone will maintain
  pregnancy if necessary

GnRH Neuroendocrine Reflex--twice
pheromone
GnRH Neuron
HYPO

GnRH
ANT PIT
stimulate sex behavior
LH FSH
LH
spinal cord
follicle
estrogen
OVARY
vaginocervical stimulation
ovulation
GnRH gonadotrophin releasing hormone FSH
follicle stimulating hormone LH luteinizing
hormone
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