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
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 female’s 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 LQ=50; this
would be considered a moderately receptive female.
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 female’s 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
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
Ovarian Cycle
There are 3 main phases of ovarian cycle:
•
follicular phase: series of hormonal events: GnRH-->LH & FSH-->estrogen
– 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-->LH surge will cause the ovarian follicle to rupture-->release 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
Ovulation and GnRH Surge in Rats:
Ovulation:
• as follicles develop in ovary
GnRH Neuron
HYPO
– increasing levels of estrogen
are released
+
GnRH
– in female rats, increases in
estrogen lead to a GnRH
surge (positive feedback)
ANT
PIT
FSH
LH
– GnRH surge leads to LH
surge
– LH surge leads to ovulation
OVARY
Estrogen
GnRH: gonadotropin-releasing hormone
FSH: follicle stimulating hormone
LH: luteinizing hormone
•
male rats are unable to show
a GnRH surge in response to
increases in estrogen
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, vaginalcervical 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”
Female Rat Estrous Cycle
•
day 1--metestrus:
– early: ovarian hormone secretion is relatively low
– late: start of follicular activity
•
follicular
phase
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
•
periovulatory
phase
luteal
phase
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
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:
•
PRL Neuroendocrine Reflex
PRF Neuron
HYPO
PRF
ANT
PIT
corpus luteum will not form unless
female engages in copulation
PRL
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
spinal cord
follicle
egg
– Ex: rats
•
+
OVARY
vaginocervical
stimulation
“corpus luteum”
forms
PRF: prolactin releasing factor
PRL: prolactin
progesterone
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-->sex 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
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) timeframe 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
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-->administration 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-->administration 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
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)-->increased
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
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-->facilitation of lordosis
– stimulate neurons within dorsolateral MPOA-->inhibition 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
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.
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.
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
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
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
LH
LH FSH
stimulate
sex behavior
spinal cord
follicle
estrogen
OVARY
vaginocervical
stimulation
“ovulation”
GnRH: gonadotrophin releasing hormone
FSH: follicle stimulating hormone
LH: luteinizing hormone
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
•
•
vaginocervical stimulation (via
intromissions from male) stimulates
further GnRH release
after ovulation, progesterone will
maintain pregnancy if necessary
pheromone
GnRH Neuron
HYPO
+
GnRH
ANT
PIT
LH
LH FSH
increasing levels of estrogen
stimulate behavioral estrus
– GnRH release will lead to LH
surge and ovulation
•
GnRH Neuroendocrine Reflex--twice
stimulate
sex behavior
spinal cord
follicle
estrogen
OVARY
vaginocervical
stimulation
“ovulation”
GnRH: gonadotrophin releasing hormone
FSH: follicle stimulating hormone
LH: luteinizing hormone