L4, L6 Flashcards
sex is based on ___ expression, ___, ___ and ___
gene, anatomy, physiology, hormones
Gender and sex differences exist in the ___, ____, __ factors, ____ and ___ response for many psychopathologies
prevalence, symptomology, risk, course, treatment
Female biased disorders include late onset _____, eating disorders such as ___ and ____, ____ and mood disorders like ____ and ____
SZ, anorexia, bulimia, PTSD, depression, anxiety
male biased disorders include ___, ____, and learning disorders like ___, as well as ___, ___ and early onset ____
ADHD, autism, dyslexia, stuttering, tourettes, SZ
There are sex differences in pain ____, as well as how people ___ pain, how a physician may understand and ___ pain depending on their own gender
sensitivity, report, treat
Gender differences exist in vulnerabilities and _____ to the impact of ____ on mental well being. In general, ___ ___ individuals report poorer mental health
resistances, stress, gender diverse
There is a false narrative that ___ ____ _____ influence facts and evidence as well as beliefs. It is misunderstood that these differences will lead to ___, ____ data.
ovarian hormone fluctuations, complicated, uninterpretable
looking at the physiology, receptors, and learning in animals found that the ___ __ ____ in males was actually greater on average than in females. Moreover, variability of behaviour, ___, ____, neurochemistry, and non brain measures found that there was non significant across ___, ___ and ___ cycles. There was no difference in variability within gender groups among different rat ___ as well
coefficient of variability, histology, electrophysiology, estrus, diestrus, proestrus, strains
Moreover, testosterone changes through the ___ and the ___ in both humans and rats. This occurs regardless of ___ ____. In rats, T increases in the ____ period and decreases in the ___ period
day, lifetime, food restriction, light, dark
Many research papers do not include ___ __ _ ___ ___, and will incorrectly determine the male brain to be the _____, and only consider females if some effect is not seen in males first
sex as a biological variable, default
when an endpoint has two distinctive forms, with one almost exclusively present in one sex vs the other
sex dimorphism
when the endpoint les along a continuum with different averages for males vs females, but much overlap
sex difference
when neural and hormonal factors act to make endpoint in males and females more similar or opposing
sex convergence / divergence
when the endpoint is the same in males vs females, but the frequency with which it occurs differs
population differences
In males, the ___ gene promotes the ___ ___ ___ that leads to testes development. The ___ gene also pushes testes development.
SRY, testes determining factor, Sox9
In females, the _____ on the ___ chromosome, will turn off the ___ gene to produce female characteristics. Moreover, turning off the TDF and sox9 does not necessarily produce fully female or male characteristics, showing that sexual differentiation in females is not ___ or the ____
beta-catenin, third, Sox9, passive, default
A series of events whereby a sexually indifferent embryo progressively acquires male or female characteristics
sexual differentiation
early embryonic life when no sex differences have developed
bipotential stage
in the bipotential stage, which is the first ___ weeks in humans, the ___ are identical and both ___ and ____ ducts are present
6, gonads, mullerian, wolffian
Sexual differentiation begins with the ___ ___ differentiating into either the ____ or ____. These drive sexual differentiation in the morphology of the ____
genital ridge, testes, ovaries, genitals
In males, the __ ____ _____ regresses the ___ duct, and presence of ____ ____ and further develops the wolffian duct. Then _____ converts testosterone to ____, which elongates the genital tubercle to become the penis
mullerian inhibiting hormone, mullerian, testosterone, stabilizes, 5-alpha-reductase, dihydrotestosterone
in females, there is no ____ hormone product by the ovaries. This causes the ____ ___ to destabilize and ____, while the mullerian duct continues to develop. ___ ___ such as ____ also suppress genes that would lead to male development and continue mullerian duct development. Then the absence of testosterone and _____ leads to the development of the clitoris from the genital tubercle
perinatal, wolffian duct, degenerate, transcription factors, COUP-TFIII, DHT
the ___ ___ is the bipotential precursor of the penis and clitoris and is homologous and _____ in XX and XY individuals in early development. It becomes recognizably different __ weeks of gestation in humans
genital tubercle, indistinguishable, 9
when testicular androgens and hormones drive the development of male-typical reproductive physiology and behaviour
masculinization
female phenotype being actively removed from the body and brain; does not necessarily lead to masculinizing behaviour
defeminization
absence of testicular androgens and hormones and active suppression of male gene expression program, which drives female typical reproductive physiology and behaviour
feminization
sex steroids are synthesized on ____, are ____, and ____ due to binding with steroid binding globulins. They directly interact with DNA at ____ sequences in a hormone-specific manner. Each family of steroid receptors binds to a specific ___ ____. The receptors can be localized in the cell membrane for ___ responses or in the cytoplasm for ___ responses
demand, lipophilic, long-lived, palindromic, DNA sequence, fast, slow
The hypothesis that gonadal hormones have differential effects on mammalian development at different life stages
organizational-activational hypothesis
According to the O-A hypothesis, the organizational period is in ______, and involves the high ___ in males and absence in females. This provides the ___ for which later hormones can exert their effects in _____ to lead to the behavioural phenotype
gestation, testosterone, blueprint, puberty
during the perinatal period in males and females, the ____ released from the hypothalamus, reaches the ___ ____ which releases LH onto receptors in the ____ (testes) or ____ (ovaries) cells. The binding of LH results in ____ and ____ activation, which results in a protein called ___ to be activated. This protein transports _____. This then converted into _____ via _____, then ____, _____, and finally _____.
GnRH, anterior pituitary, leydig, theca, cAMP, PKA, star, cholesterol, prenenolone, P450, progesterone, androstenedione, testosterone
____ and ___ can be converted into each other by ____ in the leydig/theca cells
androstendione, testosterone, 17beta-HSD
GnRH from the hypothalamus also releases _____ via the anterior pituitary, which binds to receptors on ___ (testes) / ___ (ovaries) cells, activates cAMP and PKA, which results in activation of _____. The testosterone / androstenedione made in the leydig/theca cells then can travel to these other cells and be converted to _____ or ____ respectively via the aromatase.
FSH, sertoli, granulosa, aromatase, estradiol, estrone
estrone and ___ can be converted to each other by ______ within the sertoli and granulosa cells
estradiol, 17beta-HSD
testosterone can also be converted to ___ via 5-alpha-reductase in thhe sertoli cells
DHT
all sex steroids enter ____ ___ to reach the brain
general circulation
in rodents, testosterone peaks ___ in the perinatal period, once around ___ and again at ____ (in males only). However, there are no peaks in ___ in the perinatal period. This surge in testosterone in the perinatal period drives ____ effects on the developing brain, and is relatively ____
twice, E18, birth, androstenedione, organizational, permanent
Mounting behaviour in female rats is only seen if both ______ exposure to T and exposure in adulthood is given. If only T in adulthood is given, there is ___ mounting. Moreover, perinatal exposure to T and ___/___ treatment in adulthood do not produce ___ in females
perinatal, minimal, estrogen/progesterone, lordosis
This perinatal exposure to T also results in very little ____ receptors in females, and more in males. In adulthood, the brain responds to circulating androgens by changing androgen ___ levels
androgen, receptor
There is more aromatase in the ____, ____, ____ and ___ of males than in females in the same regions. These are the regions that are __ ___ in adulthood. Giving neonatal ____ treatment masculinized females to male-typical ___ expression. This shows that all the effects of sexual differentiation of the brain is driven by ____, not testosterone
BNST, VMH, mPOA, CeA, sexually dimorphic, estrogen, aromatase, estradiol
Kisspeptin neurons are located in the ___ ___ region of the hypothalamus, and in the presence of ____ facilitate production of ____, ___ and ____. In males, there is an increase in kisspeptin neurons at ___ and in the perinatal period. The testosterone in males is converted to ____ which combined with kisspeptin, results in more GnRH, LH, and FSH, which results in more testosterone, making a __ ____. Moreover, the _____ surge in T correlates withe sexually dimorphic expression of kisspeptin
rostral periventricular, estradiol, GnRH, LH, FSH, birth, estradiol, positive feedback, perinatal
In females, ovarian hormones are not produced, and they are also actively prevented from entering the ____ by _____, which binds to ____ and prevents its transport from the placenta to the fetus. In female mice lacking AFP, there is an absence of ____
fetus, alpha-fetoprotein, estradiol, lordosis
For females rats, if gonads are removed during puberty, male-typical behaviour is only seen they are injected with ____ before day 10, their gonads are removed, and they are injected with testosterone in ____
10, testosterone, adulthood
in male rats, male typical behaviour is only seen when the gonads are ___ in puberty, and they are injected with testosterone in _____. If the gonads are removed before day 10 (puberty), male typical behaviour can develop only if testosterone is injected in _____, and in _____
intact, adulthood, before puberty, adulthood
In theory, sensitive windows of neural development should be most likely to occur during periods of rapid _____ change, such as ____,
developmental, adolescence
In Schultz’ study, males GDX ___, showed less mounting than males GDX _____, even when given the same 7 days of T treatment in _____. T wasn’t able to rescue mounting even when given for ____ days. Moreover, males GDX pre-puberty and given ____ and ___ treatment in adulthood were faster in initiating lordosis than males GDX post-puberty. However, lordosis ___ was unaffected in all groups. Females GDX _____ served as a control/comparison group
Pre-puberty, post-puberty, adulthood, 17, estradiol, progesterone, duration, post-puberty
Another study showed that if male animals were castrated before puberty and given T _____ to puberty or _____, it would rescue mounting behaviour. However, there was no rescuing effect if the exposure was ____. There was also a greater effect when ____, suggesting that T ___ decreases in adolescence.
prior, on-time, late, early, sensitivity
The medial preoptic area in the hypothalamus, the ____ is larger in males, while the ____ is larger in females.
SDN, AVPV
The BNST is ___ and sends more ___ to the AVPV in males. the ___ ____ is also sexually dimorphic
larger, projections, medial amygdala
In juvenile animals that were castrated before puberty and given no T treatment, they had decreased ____, _____, ____, ____, and ___ volume, and increased ____ volume in comparison to a normally developed adult animal castrated ___ puberty and given T treatment throughout adulthood. Giving pre-pubertal T treatment to the juvenile rats increased the size of the _____, ___, ___ and ___, but did not affect the ___ or ___ volume
SDN, BNST, VMH, MePD, MePV, MeAD, after, SDN, BNST, MePD, MePV, VMH, MeAD
It was shown through many experiments that early life testosterone can _____ male typical behaviour in ___ animals, and produce ____ changes that may underlie those behaviours
rescue, castrated, morphological
In typically developed mice, females have more _____ _____ expressing neurons in the ____, ___, ___ and ___ ___ of the hypothalamus. Males have more of those neurons in the ___ ___ and the ___. This is why progesterone given to typically developed females will produce ____, but will not to the same extent in males. Moreover, females exhibit denser projections of these neurons in the ___ to the ____ than males.
progesterone receptor, AVPV, POA, VMH, arcuate nuclei, posterior VNST, MePD, lordosis, VMH, AVPV
females lacking the progesterone receptor expressing neurons in the _____ exhibited fewer female typical ___ ____ and greater male typical sexual behaviour than controls. They spent more time ___ males, had lower ____, lower ___ and ___ of lordosis, and more ___. Thus, changes due to gonadal hormones in adolescence may ___ progesterone receptor expressing neurons to be activated in different ways in adulthood by ___ and ____
VMH, sexual behaviours, rejecting, receptivity, duration, frequency, mounting, prime, testosterone, progesterone
In primates, testosterone treatment was successful in rescuing ____ behaviour in males only if castration occurred ___. This effect was not seen if they were castrated ____.
tongue-flicking, pre-pubertally, neonatally
In tree shrews, males exhibit more marking behaviour than females in the ___ of any conspecific scent. In the presence of a ___ scent, there is low marking in both sexes. In the presence of a male scent, ___ exhibit more marking behaviour. Their puberty onset is also at ___ weeks of age
absence, female, females, 5
If male tree shrews are GDX in _____, they show an increase in marking events in response to a ___ scent, just like regular females. This effect is not seen if they are treated with T in _____. the controls were a male GDX in ___, and a ___. Moreover, this effect is not seen for ____ marking. This group also shows ____ to the male scent just like the females, while the effect disappears again if treated with testosterone in puberty.
juvenility, male, puberty, adulthood, female, territorial, habituation
In rats, the emergence of male ____ is not perfectly correlated to increases in T in ____
aggression, puberty
In mice, the increasing days of T treatment required to exhibit aggresion from lowest to greatest is: only ____ absence of T, only _____ absence of T, and absence of T in both ____ and ____. This was in female and male animals GDX at ____. However, it showed that ____ T in both females and males can induce aggressive behaviour regardless of ____ treatment
prenatal, neonatal, prenatal, neonatal, birth , adult, prenatal
If female animals are castrated in ____and given ____ mg of T, they exhibit high aggression similar to males. However, this effect is not seen for females initially only given ___ mg of T. Moreover, the first group maintained this effect even when switched to a 0.3mg T ____
adulthood, 10, 0.3, transplant
In typically developed adult rats, ___ exhibit more anxiety behaviour than _____. If ____ T is given to females, they exhibit more anxiety on the elevated plus maze and ___ ___ ___, suggesting the prenatal _____ seem to exert organization effects on sex-typical anxiety behaviours
males, females, prenatal, open field test, androgens
drugs that inhibit conversion of testosterone to estradiol
aromatase inhibitors
1,4,6-androstatriene-3,17-dione
aromatase inhibitors
drugs that modulate actions of estrogens or androgens at their receptors, either enhancing or inhibitng their biological effects depending on the tissue
selective estorgen/androgen receptor modulators (SERM) / (SARM)
tamoxifen
inhibitory SERM
flutamide
inhibitory SARM
drugs that bind to estrogen or androgen receptors and degrade them
selective estrogen / androgen receptor degraders (SERD) / (SARD)
fulvestrant
SERD
dimethylcurcumin
SARD
You can also use treatments with an androgen that doesn’t convert to estradiol like ___, or ____ animals that have mutations in their genes that ___ androgen or estrogen receptors (ex. ___)
DHT, transgenic, transcribe, tfm
Transgenic male animals with dysfunctional ___ receptors do not show any change in ____ from their WT counterparts, showing it is not this receptor that is driving sex differences in anxiety
androgen, anxiety
When androgen receptors are blocked in ____ mice, they still show male typical anxiety, suggesting that ____ is driving this effects. Moreover, _____ ____ also had no effect on anxiety
male, estrogen, pre-puberty castration
in females, prepubertal _____ or neonatal blocking of ____ receptors was sufficient in driving male typical phenotype for anxiety, suggesting that ____ matters in females in producing lower anxiety, and that neonatal exposure to _____ may drive the effect despite being minimal
GDX, estrogen, puberty, estradiol
In males, GDX in either ___ or _____ produced a female typical pattern of anxiety, while GDX in adulthood produced ___ ___
juvenility, mid-adolescence, no effect
Another study found that giving males ___ ___ or ___ ____ in adulthood after GDX in early adolescence did not produce a change in anxiety
acute estradiol, acute T
____, ___ and progesterone metabolites can bind directly to ___ receptors to alter GABA signalling. GABA releasing ___ also express ____ receptors, upon which estradiol can exert modulatory effects. Thus, ___ and ____ estradiol effects on anxiety like behaviours may be driven by GABA-ergic modulation
estrogens, progesterone, metabolites, GABA-A, interneurons, estrogen, perinatal, pubertal
A male typical behaviour is novelty induced ___ ____. If males are GDX in ___, they do not show this anxiety, while if they are treated with ___ in adolescence, they show it again. Males GDX in adulthood show social anxiety, suggesting ____ ___ is not responsible for social anxiety behaviours
social anxiety, juvenility, T, adult T
___ which enhances the function the GABA-A receptor, abolishes male typical ___ ____. However, if the animals are castrated in juvenility, they ___ social anxiety, even if given ____. If these rats are given T in ____ the social anxiety is again abolished. This suggests that ___ in prenatal or puberty period can act on _____ receptors to alter the system
diazepam, social anxiety, show, DZ, puberty, estradiols, GABA
glycoprotein that binds to androgens and estrogen, allowing them to circulate in the bloodstream and simultaneously limit their entry into cells
sex hormone binding globulin
in humans, men have more circulating ___ than women, while there are no differences in ___ concentrations. Women have more ___ than men, suggesting they limit ___ ___ from entering cells more than men.
T, androstenedione, SHBG, sex steroids
High T in men was associated with ____ ___, while in women, androgens and SHBG were ___ to anxiety disorders
anxiety disorders, unrelated
People with klinefelter’s syndrome are _____ chromosome males, with smaller ____, and lower production of ___. These people show ___ anxiety disorder prevalence
XXY, testicles, T, higher
Women with PCOS have ovaries that produce high levels of ____. They show ___ prevalance of anxiety disorders
androgens, higher
Men with _____ ____ ___, have a GnRH deficiency, leading to low T production. They show lowered anxiety if given ___ treatment.
congenital hypogonadotropic hypogonadism, T
in females, ___ androgens seem to increase anxiety, while in males, low ___ seems to increase anxiety. it is possible that hormonal impact is ___ shaped,
high, testosterone, U
prenatal estrogen and androgens may drive sex differences observed in adult hippocampus ____ and ____ ___. Normally, the ___ and ___ of the hippocampus is bigger in males than in females. Prenatal _____ or ____ makes the CA1 bigger in females, while only prenatal ____ make the CA3 bigger in females
morphology, spatial memory, CA1, CA3, androgens, estradiol, estradiol
When animals are tested in the morris water maze, females given prenatal _____ and ___ are faster than controls, while males with blocked ___ ___ in the prenatal period show slower escape latency. This suggests that androgens drive sex differences in spatial memory but only in the ____ ____.
testosterone, DHT, androgen receptors, prenatal period
In humans doing a ___ morris water maze task, females with __ __ ___, a genetic disorder that causes in utero excess androgen production, show ___ escape than female controls, similar to that of ____ ____ or males with CAH. This effect was greatest for females with the most ___ form of the disorder and thus ___ level of in utero exposure to androgens. This suggests that in utero exposure to androgens have ____ effects on cognitive function
virtual, congenital adrenal hyperplasia, faster, healthy males, severe, highest, long-lasting
The two stage O-A model proposes that there is prenatal period of ___ __ ______, then a steroid-dependent ___ ___ during puberty and adolescence. This second peak is acting on the previous ______ in the perinatal period. These _____ structural changes determines the ___ ____ responses to hormones and ______ stimuli
steroid-dependent sexual differentiation, neural organization, organization, long-lasting, adult behaviour, socially-relevant
Because ____ to organizing actions of T ____ with time, differences in the ____ of pubertal onset may result in differences in ___ ___ and adult behaviour
sensitivity, decreases, timing, brain development