Transcript Document

Males
Hypothalamus→GnRH→
Pituitary→LH→Testes→Testosterone
The level of testosterone is under negative-feedback
control: a rising level of testosterone suppresses the
release of GnRH from the hypothalamus. This is
exactly parallel to the control of estrogen secretion in
females.
Males
Males need estrogen, too!
In 1994, a man was described who was homozygous
for a mutation in the gene encoding the estrogen
receptor. A single nonsense mutation had converted a
codon (CGA) for arginine early in the protein into a
STOP codon (TGA). Thus no complete ER could be
synthesized.
This man was extra tall, had osteoporosis and "knockknees", but was otherwise well. His genetic defect
confirms the important role that estrogen has in both
sexes for normal bone development.
Males
It is not known whether this man (or any of the few
other men who have been found with the same
disorder) is fertile or not.
However, an article in the 4 December 1997 issue of
Nature reports that male mice whose ER gene has
been "knocked out" are sterile.
Males
Anabolic steroids
A number of synthetic androgens are used for
therapeutic purposes. These drugs promote an increase
in muscle size with resulting increases in strength and
speed. This has made them popular with some athletes
(weight lifters, cyclists, runners, swimmers, professional football players).
Usually these athletes (females as well as males) take
doses far greater than those used in standard therapy.
Such illicit use carries dangers (besides being banned
from an event because of a positive drug test): acne, a
decrease in libido, and — in males — testicle size and
sperm counts to name a few.
Males
Genetic abnormalities of gonadal function.
Many things can go wrong with sexual development in
both males and females; fortunately rarely. only at a
few that clearly result from the inheritance of singlegene mutations.
Inherited mutations in both copies of the gene
encoding the GnRH receptor result in failure to
develop at puberty.
Mutations in the gene encoding the LH receptor
prevent normal sexual development in both sexes.
Males
Genetic abnormalities of gonadal function.
Mutations in the gene encoding the FSH receptor
block development of the gonads in both males and
females.
Mutations in any of the genes encoding the enzymes
for synthesis and metabolism of testosterone interfere
with normal sexual function in males.
A similar spectrum of disorders in males can be caused
by mutations in the genes encoding the androgen
receptor.
Females
The ovaries of sexually-mature females secrete:
a mixture of estrogens of which 17β-estradiol is the
most abundant (and most potent).
progesterone.
Females
Estrogens
Estrogens are steroids.
primarily responsible for the conversion of girls into
sexually-mature women.
development of breasts
further development of the uterus and vagina
broadening of the pelvis
growth of pubic and axillary hair
increase in adipose (fat) tissue
participate in the monthly preparation of the body for a
possible pregnancy
participate in pregnancy if it occurs
Females
Estrogens also have non-reproductive effects.
They antagonize the effects of the
parathyroid hormone, minimizing the loss of
calcium from bones and thus helping to keep
bones strong.
They promote blood clotting.
Females
Progesterone
Progesterone is also a steroid. It has many effects
in the body, some having nothing to do with sex and
reproduction.
Is important in menstrual cycle and pregnancy
How estrogens and progesterone achieve their
effects
Steroids like estrogens and progesterone are small,
hydrophobic molecules that are transported in the
blood bound to a serum globulin.
In "target" cells, i.e., cells that change their gene
expression in response to the hormone, they bind to
receptor proteins located in the cytoplasm and/or
nucleus.
The hormone-receptor complex enters the nucleus
(if it formed in the cytoplasm) and
binds to specific sequences of DNA, called the
estrogen (or progesterone) response elements
How estrogens and progesterone achieve their
effects
Response elements are located in the promoters of
genes.
The hormone-receptor complex acts as a
transcription factor (often recruiting other
transcription factors to help) which
turns on (sometimes off) transcription of those
genes.
Gene expression in the cell produces the response.
Regulation of Estrogen and Progesterone
The synthesis and secretion of estrogens is
stimulated by follicle-stimulating hormone (FSH),
which is, in turn, controlled by the hypothalamic
gonadotropin releasing hormone (GnRH).
Hypothalamus→GnRH→
Pituitary→FSH→Follicle→Estrogens
Hermaphroditism is a term referring to being of both
sexes (intersexual).
True hermaphroditism requires the presence of both
ovarian (female) and testicular (male) reproductive
tissue and is relatively rare and poorly understood.
Pseudo-hermaphroditism is more common.
From a medical standpoint, hermaphroditism
suggests two factors:
ambiguous external genitalia
genitalia that do not match the genetic make-up of
the person (example: female genitalia in a genetically
male individual)
The following conditions can produce ambiguous
genitalia and hermaphroditism:
congenital adrenal hyperplasia
fetal exposure to sex hormones
testicular feminization syndrome
XY gonadal dysgenesis
XY gonadal agenesis
chromosomal abnormalities
cryptophthalmos
Smith-Lemli-Opitz
4p syndrome
13q syndrome
Congenital adrenal hyperplasia refers to a
group of inherited disorders relating to the
adrenal glands, characterized by a deficiency in
the hormones cortisol and aldosterone and an
overproduction of androgen.
Alternative Names: Adrenogenital syndrome;
21-hydroxylase deficiency
Congenital adrenal hyperplasia
Causes, incidence, and risk factors:
The different types of adrenogenital syndrome are
inherited as autosomal recessive diseases and can
affect both boys and girls.
The defect is lack of an enzyme needed by the
adrenal gland to make the major steroid hormones
of the adrenal cortex: cortisol and aldosterone. Due
to the block in synthesis of these hormones, there is
abnormal 'feedback' and steroids are 'diverted' to
becoming androgens, a form of male sex hormones.
Congenital adrenal hyperplasia
This causes early appearance of male characteristics. In a newborn
girl with this disorder, the clitoris is enlarged with the urethral
opening at the base (ambiguous genitalia, often appearing more
male-like than female). The internal structures of the reproductive
tract (ovaries, uterus, and fallopian tubes) are normal. As she grows
older, masculinization of some features takes place, such as
deepening of the voice, the appearance of facial hair, and failure to
menstruate at puberty.
In a newborn boy no obvious abnormality is present, but
long before puberty normally occurs, the child becomes
increasingly muscular, the penis enlarges, pubic hair
appears, and the voice deepens. Affected males may
appear to enter puberty as early as 2-3 years of age.
At puberty, the testes are small.
Congenital adrenal hyperplasia
Some forms of congenital adrenal hyperplasia are
more severe and cause adrenal crisis in the
newborn due to salt wasting. In this salt-losing
form of congenital adrenal hyperplasia, newborns
develop symptoms shortly after birth. These
include vomiting, dehydration, electrolyte changes,
and cardiac arrhythmias. Untreated, this condition
can lead to death within 1-6 weeks after birth.
About 1 in 10,000 to 18,000 children are born with
congenital adrenal hyperplasia.
Turner syndrome
A disorder in women caused by a chromosomal
defect. This disorder inhibits sexual development
and causes infertility.
Alternative Names:Bonnevie-Ullrich syndrome;
Gonadal dysgenesis; Monosomy X
Causes, incidence, and risk factors:Turner
syndrome is usually caused by a missing X
chromosome. It affects 1 out of 3,000 live births. It
is usually sporadic meaning that it is not inherited
from a parent.
Turner syndrome
Rarely, a parent silently carries rearranged chromosomes
that can result in Turner syndrome in a daughter; this is
the only situation in which Turner syndrome is inherited.
There are many manifestations of this syndrome, but the
main features are short stature, webbing of the skin of the
neck, absent or retarded development of secondary sexual
characteristics, absence of menstruation, coarctation
(narrowing) of the aorta, and abnormalities of the eyes and
bones.
The condition is either diagnosed at birth because of the
associated anomalies, or at puberty when there is absent or
delayed menses and delayed development of normal
secondary sexual characteristics.
Ambiguous genitalia
A congenital physical abnormality where the outer
genitals do not have the typical appearance of
either sex.
Considerations:The genetic sex of a child is
determined at conception. The egg cell (ovum)
contains a chromosome called the X chromosome.
Sperm cells contain either an X chromosome or
one called the Y chromosome. These determine
the child's genetic sex. Normally an infant will
inherit ONE PAIR (one from the mother and one
from the father) of these "sex chromosomes" (two
chromosomes).
Ambiguous genitalia
Thus, it is the father who "determines" the genetic sex of
the child. An infant who inherits the X chromosome from
the father is a genetic female (XX pattern) and one who
inherits the Y chromosome is a genetic male (XY
pattern).
The reproductive organs and genitals associated with
"female" or "male" arise from the same initial (fetal)
tissue. If the process that causes this fetal tissue to
become "male" or "female" is disrupted, ambiguous
genitalia can develop.
Ambiguous genitalia
Ambiguous genitalia are those in which it is difficult to classify the
infant (by physical examination) as male or female. The extent of
the ambiguity varies. In very rare instances, the physical
appearance may be fully developed as the opposite of the genetic
sex (e.g., a genetic male may have normal female appearance).
Typical ambiguous genitalia in genetic females include an
enlarged clitoris that has the appearance of a small penis.
The urethral opening (where urine comes out) can be
anywhere along, above, or below the surface of the
clitoris, which may be considered normal or common
abnormalities of anatomic urethra placement (such as
hypospadias, when the urethra is on the underside of the
penis, instead of at the tip).
Ambiguous genitalia
The labia may be fused, resembling a scrotum.
The infant may be thought to be a male with
undescended testicles; sometimes a lump of tissue
is felt within the fused labia, further making it
look like a scrotum with testicles.
Ambiguous genitalia
In a genetic male, findings of ambiguous genitalia include a small penis,
less than 2 to 3 centimeters (0.8 to 1.2 inches) that may appear to be an
enlarged clitoris (the clitoris of a newborn female is normally somewhat
enlarged at birth). The urethral opening may be anywhere along, above,
or below the penis; it can be placed as low as on the peritoneum, further
making the infant appear to be a female. There may be a small scrotum
with any degree of separation, resembling labia. Undescended testicles
commonly accompany ambiguous genitalia.
Uncertain or mistaken sex is not a physical threat to life, but can create
social upheaval for the child and the family.
Ambiguous genitalia
Common Causes:
pseudohermaphroditism (when the genitalia are of one
sex, but some physical characteristics of the other sex
are present)
true hermaphrodism (very rare -- both ovarian and
testicular tissue is present and the child may have parts
of both male and female genitalia)
mixed gonadal dysgenesis (where some cells in the
body have only a single X chromosome-->female, and
some cells in the body have XY chromosomes-->male.
This syndrome is variable, and depends on which cells are
female, which cells are male, and what percent of each there
are
Ambiguous genitalia
Common Causes:
congenital adrenal hyperplasia (several forms, but the
most common form causes the genetic female to
appear male. Male infants with the most common form
appear normal at birth, but may show premature
sexual development as early as 6 months of age) -many states test for this as part of the newborn screen
(the blood test your baby has at 24-48 hours of life)
chromosomal abnormalities including
Ambiguous genitalia
Common Causes:
Klinefelter's syndrome (XXY--male, usually has
small testes; causes infertility; may be associated
with learning defects or mental retardation; affects
1/500-1/1000 live male births)
Turner's syndrome (XO--female; usually does not
cause ambiguous genitalia (usually looks female at
birth), but may have webbed neck, swelling of the
hands and feet and other characteristic physical
findings at birth; may not be diagnosed until later in
life when sexual maturation does not take place;
infertile)
Ambiguous genitalia
Common Causes:
maternal ingestion of certain medications (particularly
androgenic steroids) -- may make a genetic female
look more male
lack of production of specific hormones, causing the
embryo to develop with a female body type regardless
of genetic sex
lack of testosterone cellular receptors (so even if the
body makes the hormones needed to develop into a
physical male, the body is unable to respond to those
hormones, and therefore, a female body-type is the
result even if the genetic sex is male)
Puberty-Time to Change
When your body reaches a certain age, your brain
releases GnRH that starts the changes of puberty.
When GnRH reaches the pituitary gland, this gland
releases into the bloodstream two more puberty
hormones: LH and FSH.
Guys and girls have both of these hormones in their
bodies. And depending on whether you're a guy or
a girl, these hormones go to work on different parts
of the body.
Puberty-Time to Change
Guys- these hormones travel through the blood and
give the testes the signal to begin the production of
testosterone and sperm.
Testosterone is the hormone that causes most of the
changes in a guy's body during puberty. Sperm
cells must be produced for men to reproduce.
In girls, FSH and LH target the ovaries, which
contain eggs that have been there since birth. The
hormones stimulate the ovaries to begin producing
another hormone called estrogen. Estrogen, along
with FSH and LH, causes a girl's body to mature
and prepares her for pregnancy.