Lecture 7 Flashcards
Sex hormones (Male and Female)
Male Sex Hormones: Androgens - Testosterone - Dihydrotestosterone - Androstenedione Major hormone class: Dehydrogenase
Female sex hormones: Estrogens - Estradiol - Estrone - Estriol - Progestins: Progesterone Major hormone class: Aromatase
All very closely related either as precursors or only one step away products
Organizational hormone action
When does it act?
What does it do?
Is it reversible?
Is it the same in men and women?
Organizational hormone action
- Pre- and early postnatal development
- Hormones ‘sculpt’ biological, neural, and behavioral systems
1. permanent and irreversible
2. can only occur during critical development periods
3. lead to permanent structural and/or physiological changes - some in other endocrine systems
4. asymmetric with regards to the sexes (Androgens needed for masculinization, estrogens are not needed for female development)
Activational hormone action
Activational hormone action
- Later in development (puberty)
- not permanent - only displayed when hormone is present (if body stops making it, action stops)
- no critical development periods, HR|T for trans women late in life changes body towards female
- more subtle changes
Prenatal Sexual Differentiation
Pre 7th week
Post 7th week (gonads)
PRE
Fertilized egg contains sex chromosomes
-female always contributes X, male either X or Y
-XX = female
-XY = male
-Embryo stays in “undifferentiated” state until 7th week
-Process of differentiation during the prenatal period
Requires sex chromosomes & sex hormones
POST
7th week: gonads to begin differentiation
-Male - develops testes at about 7 weeks
-Sex-determining region – SRY (Sex determining region)0
-manufacture of TDF (testis determining factor)
-Female - ovaries develop at around 10-11 weeks
-Occurs in absence of hormones, suggests female is default
-X chromosome – effects on development of cells in the ovaries and cells in the testes and so has effects in both sexes. Y only on males
Mullerian and Wolffian ducts
Mullerian (paramesonepheric) and Wolffian
(mesonepheric) ducts in both male and female fetus
Males
-Testes produce anti-Mullerian hormone (Stertoli cells)
and T (Leydig cells)
-Wolffian ducts – develop because of T
-anti-Mullerian hormone degrades Mullerian system
- Females
- Wolffian degenerate without androgens
- Mullerian remain in the absence of anti-Mullerian hormone
Genital development in males
Test causes the Wolffian duct to become the internal genitals
The urogenital sinus develops in to external genitals. This is not developed by testosterone
Rather this is reduced by 5-alpha-reductase to DHT and this causes external genitalia
Genital development in Females
The urogenital sinus in the absence of androgen exposure develops into the external genitalia (lower vagina)
The Mullerian ducts develop into the internal organs (most of the upper vagina, cervix, uterus, fallopian tubes
Homologous vs Analogous organs
Homologous organs develop from the same embryonic
tissue
Analogous organs have similar functions
Ovaries and testes are both
Scrotum and labia re homologous but not analogous
Homologous vs Analogous organs
Homologous organs develop from the same embryonic
tissue
Analogous organs have similar functions
Ovaries and testes are both
Scrotum and labia are homologous but not analogous
Species and sex devlopment
In mammals SRY and TDF cause testes to develop
-Then T causes differentiation
In reptiles, SRY is present but temperature contributes
Birds: Male have ZZ chromosome and females WZ (default setting male)
Human psychosexual differentiation
Happens very young
- Babies at nine month capable of discriminating between the sexes
- Children soon learn to identify their own gender, and understand that it is stable, likely because we socialize them (probably social rather than biological)
-Effect on gender roles and gender identity
Sexual differentiation at puberty
Period of relative hormonal inactivity during childhood
Dramatic surge of HT hormones prior to and during puberty
GnRH -> LH, FSH ->
men: Leydig cells: testosterone
women: thcea and granulosa cells: estradiol
Adrenal cortex: DHEA, Androstenedione as puberty approaches
6-7 in females, 7-8 in males
Secondary sexual charecteristics
Males: Spermarche: viable sperm produced
Females:
Thelarche: breast development
Menarche: first menstruation
Both:
Adrenarche: androgens from adrenal glands
Pubarche: pubic hair growth
Puberty and GnRH
Puberty and GnRH
GnRH Neurons
-Gonadotrophin Releasing Hormone (GnRH) neurons in preoptic area of hypothalamus
-Secrete GnRH into median eminence to anterior pituitary
There is an increase in GnRH neurons in the MPOA during puberty
-Increases in GnRH maintained throughout reproductive period
Not entirely clear why
Sexual differentiation at puberty
Morph sex
Orientation
Morphological sex: men are larger and stronger while women have more adipose tissue deposits
Sexual orientation: males are most commonly attracted to females, and vice versa (this might have happened earlier than this but it becomes apparent at this age)
Behaviour begins so distinction becomes more obvious
Gender roles and gender identity: inner conviction about their gender (which may or may not align with biological sex)
Exists before puberty, but may be exacerbated
Estrus and lordosis
Female rats attack males who try to mate with them if they are not in estrus
If they are they do lordosis which allows mating
Organizing action of prenatally administered testosterone on guinea pigs experiment (Basics)
Guinea Pig mothers repeatedly administered T during pregnancy. This mimics the testosterone surge during male development
Gonadectomized all babies early in life (removed all gonads so it is juts their hormones that affect things)
IN ADULTHOOD: Estradiol (E2) and progesterone (P) to stimulate female sexual behaviour
IV=hormonal condition (one condition of 4)
DV = Sexual behaviour
In this case this is Lordosis to manual stimulation (which simulates what a G pig would do measured 3 ways
Originally they administered 3 different dose levels of testosterone to the mothers while they were pregnant but this was not needed as they
Organizing action of prenatally administered testosterone on guinea pigs experiment (IV groups)
There were 4 groups
1 Control females
No administration of testosterone to their mothers
2 Unmodified females
Test administered to mother, still biologically female at birth
3 Hermaphrodites
Test administered to their mother
Had shown masculinization and now had a mixture of male and female sexual characteristics
4 - Castrated males
Phenotypically male, castrated after birth
Effectively, these groups measure increasing levels of masculinization as a result of prenatal hormone levels (and in group 4, chromosomes)
Organizing action of prenatally administered testosterone on guinea pigs experiment (Results)
DV measured as after the administration od estrodiol and progesterone;
-Percentage that did lordosis
More androgenization = less percentage that did lorsosis
-Mean time it took following administration of estradiol and progesterone before GPig did lordosis
More androgenization = longer time to do lordosis
-Mean duration of heat (how long will manual stimulation result in lordosis)
More androgenization = less time receptive to doing lordosis
-How long will they do max lordosis in seconds
More androgenization = less time at max lordosis
SUMMARY
Administration of testosterone to pregnant dams
means female offspring:
May not develop complete female genitalia
Reduction in female typical sexual behaviour in
adulthood
Similar to castrated male
Prenatal testosterone masculinizes sex organs and
behaviour
Can occur up to post natal day 9
Estradiol can also masculinize a rodent
Estradiol administered as control for T (review McCarthy, 2008)
- Higher masculinizing effects than testosterone!?!?
- Aromatase: transforms testosterone into estradiol
Found by accident, sued estradiol as a control. Though this would not masculinize, did. Testosterone can be converted to estradiol (E2) via aromatase
-Some masculinization to testosterone
is via E2!
-E2 absent in the developing female; ovaries
do not produce any hormones until puberty
-Blocking aromatase blocks some
masculinization –E2 is important in
masculinization
Test influence on the sexually dimorphic nucleus of the POA of male and female rats
Like before, the change in the POA seen in rats exposed to test also happens to rats exposed to estradiol
Maternal stress during pregnancy
Adrenals mostly make stress hormones due to their enzyme rations but do make androgens. High levels of stress can cause this.
Female rodents whos mother experienced significant stress were less likely to do lordosis and spent less time doing it
Male offspring who’s mothers experienced stress take a longer time to mate and a longer time to ejaculate
IN HUMANS maternal stress is associated with less fertility
Also changes the anogenital distance. Typically this is longer in men and shorter in women. Women born to stressed mothers have longer gaps.
Therefore:
- High adrenal activation results in higher androgen levels in females
- Higher adrenal activation reduces androgen exposure in males
- Early life stress alters gonadal hormone balance altering organization
IN HUMANS
Estrogens masculinize in
humans??
Maternal estrogen in pregnancy - maintain pregnancy, correlates with aspects of development
Why all females not masculinized??
In rats alpha-fetoprotein binds estrogens to prevent crossing the blood-brain barrier
Motta-Mena & Putts, 2017
In humans AFP does not bind estrogen in the same way
In humans estrogen do not masculinize?
Men with genetic disorders of aromatase (no estrogen) develop “typically male”
Men with no androgen receptors still have estrogen receptors but no masculinization
Primates treated with testosterone and DHT same masculinization but DHT CANNOT be converted into estradiol indicating this hormone is not needed for masculinization
Luoto & Rantala, 2018
Steroid Binding Globulin serves a similar function in adult humans –protect female fetus?
Estrogen masculinizes humans, similar to rodents?
Mixed evidence that estrogen treatment to pregnant mothers = elevated homosexuality and altered genitals
Motta+Putts evidence in men with genetic disorders – not typically developing males… can you generalize this to others?
Mini puberty!
What is it and what does it do?
At birth gonads are inactive
At ~2-3months 2nd mini-puberty: gonads are active and producing hormone
This seems to be important for:
- Genital development: testes, penis, mammary gland and uterus growth + male fertility
- Body development: testosterone neg. correlation to adipose
- Cognitive development: test neg. estradiol pos. correlation to measures of language
- Clear that female fetus’ and infants exposed to estrogens
May not prove that estrogens do NOT masculinize, could be an issue of timing
Nongenomic techniques
Behavioral effects of hormone that are not genetically mediated
3 Biases with behavioral endocrinology
1 - Anthropomorphic attribution (eg bird song)
2 - What are relevant behaviors
3 - Must thoroughly describe behavior (eg when does it sing etc)
2 Ways behavior is described
Descriptions of action - animal behavior described with no reference to the effects of behavior on the environment (song birds singing)
Descriptions of consequence - describes effects of behavior on the environment (made a nest)
Simple systems method
Use small genetically identical animals (like knockout mice) to infer the hormonal effects in humans as you cannot account for the cofounds in humans
Raises issues of ecological validity
Might not apply to other species/humans
How/Why levels of explination
Proximate
Ultimate
What do hormones do behaviorally
Change the probability of specific behavior
Different types of sex (4)
Hormonal sex - ratio of estrogens to androgens
gonadal sex - what gonads dominate
Morphological sex - difference in body type by sex
Behavioral sex - sex based behavior differences (eg females’ chooses mate in mammals)
Intersexual selection
one sex chooses another
Intrasexual sex
one sex competes with another of its sex for something
The sex that chooses is usually
smaller with less Intrasexual differences
Turners syndrome
X0
Sexed as girls Partial ovary development Need horomes to hit puberty Many other effects Usually in girls, XX, one X gets turned off
CAH
Increased androgens from adrenal gland
Masculinizes girls
Androgen insensitivity
SRY gene - testes develop and male hormones
Is anti mullerian
But no response to androgens
Wolfian duct does not grow
Sexed as female, short vagina and infertile
5-apha-reductase
XY, no 5-alpha-reducatase
Ambiguous genitals, small undescended testicles
Test masculinizes them at puberty but they were sexed and raised a s a girl and have low fertility
Klinefelter syndrome (XXY)
Y=testes develop
Not much masculinization (sterile as they have low sperm)
Learning is affected
XXY
Sterile men
Tall
Less intelligent
Much more in prison (but not more aggressive)
If you give prenatal androgens to rats
born with male genitalia
Free martins
XY female borne as twin to men
Female external genitals
Gonads atrophied
Theories that androgens in male twin reach female and change her
When anastomoses are obliterated = no masculinization
Control of ovulation
Pulsatile GnRH leads to increased estrogen
Estrogen levels increase in blood
Causes a strong surge in GnRH (Positive feedback)
Increases LR and FSH
Causes ovulation
Returns to normal release
Only happens in females
Why does GnRH positive feedback not happen in males?
Change in hypothalamus in development
Early androgen surge
How does positive feedback happen in ovulation
Pulsatile release of GnRH is in the VM nuclei and arcuate nucleus
Produces daily surge of GnRH
If that coincides with high circulating estrogen levels
Get a massive GnRH surge
Causes LH surge
Masculinization destroys these pathways
Estrogen and masculinization
Test is converted to estrogen in the brain
Changes brain
Injections of estrogen to rats under 10 days old masculinizes more than test
Steroid receptors and musculinization
3 day old rats
block estrogen receptors in brain
give test
ovariectomized and given est and progest
100% of control did lordosis
20% of those who got test and no blocker did lordosis
80% of those that got test and estrogen blocker did lordosis
SO blocking estrogen signaling affected the masculinization effects of testosterone (est is needed for masculinization)
Receptor subtypes
Can cause differing patterns of masculinization
