Neuroendocrine control of the reproduction process.

Gender differentiation of the brain and behavior.

 GnRH neurons, or gonadotropin-releasing
hormone-expressing neurons, are brain cells that
control the release of reproductive hormones from
the pituitary gland. These brain cells control
reproduction by secreting GnRH into the portal
capillary blood stream of the pituitary gland, so they
are sometimes called "sex neurons".

GnRH activates its own receptor, the gonadotropin-

releasing hormone receptor (GnRHR), a seven-
transmembrane G-protein receptor that stimulates the
beta isoform of phosphoinositide-phospholipase C,
which continues to mobilize calcium and protein kinase
Fluorescent image of
C. This leads to the activation of proteins involved in the
GnRH neurons (blue) with
synthesis and secretion of gonadotropins LH and FSH.
elements of their cellular
GnRH is degraded by proteolysis within minutes. cytoskeleton shown in red
and green.
 In the pituitary gland, GnRH stimulates
the synthesis and secretion of follicle-
stimulating hormone (FSH) and
luteinizing hormone (LH).
These processes are controlled by the size
and frequency of GnRH pulses, as well as
feedback from androgens and estrogens.
Low-frequency GnRH pulses are necessary
for the release of FSH, while high-
frequency GnRH pulses stimulate LH
pulses to each other.

There are differences in the secretion of GnRH in women and men.

In men, GnRH is secreted in pulses with a constant frequency; however, in women,
heart rate changes throughout the menstrual cycle, and there is a large spike in
gonadoliberin just before ovulation.

GnRH secretion is pulsatile in all vertebrates and is essential for proper reproductive
function. Thus, a single hormone, GnRH, controls the complex process of follicular
growth, ovulation and maintenance of the corpus luteum in women and
spermatogenesis in men.
The brain-pituitary-gonadal axis: GnRH is
secreted by GnRH neurons in hypothalamus
and preoptic area. GnRH stimulates
gonadotropes in anterior pituitary to secrete
gonadotropins i.e. LH and FSH.
Gonadotropins act on the gonads i.e. testis
and ovary which secrete sex steroids like
androgens, estrogens and progestins. The sex
steroids, under proper stimulus, show
negative feedback on anterior pituitary,
hypothalamus and preoptic area during most
of the cycle. But during some stages as in
menstrual cycle, sex steroids may also show
positive feedback on anterior pituitary and
hypothalamus, causing hormonal surge. The
Inhibin B secreted by the Sertoli cells in testis
show negative feedback on anterior pituitary
and hypothalamus. GnRH -Gonadotropin
releasing hormone; LH -Luteinizing hormone;
FSH -Follicle stimulating hormone;
 Further
Gender determination begins with chromosomes.
production of In mammals, males and females
hormones during have 22 autosomes in common,
puberty but differ in one set called the sex
chromosomes, X and Y

the Sry gene is an

important trigger for
The second period of In the absence of Sry, male sex determination
steroidogenesis begins during the developmental
the second half of pregnancy, program defaults to the
and it is this period of hormone female
production that is the main one
for the brain.
Formation of the Wolff ducts
? Or ?
Müller ducts
Additional production of gonad-specific hormones
during peripuberty results in a definitive male or
female phenotype.
 The production of androgens and estrogens, the so-called sex
steroids or gonadal steroids, begins with the active transport of
cholesterol into cells by StAR (steroidogenic acute regulatory protein)
and subsequent enzymatic transformations, which usually reduce the
size of the previous precursor molecule by cleavage of the side chain.
(scc). The androgen, testosterone, can be either 5a-reduced to
dihydrotestosterone, which is the final active metabolite in this pathway,
or aromatized to estradiol, which is the final active metabolite in this
pathway.

Estradiol binds to the estrogen receptor (ER), which is located either in the
membrane or in the cytoplasm. After binding, the receptors homodimerize in the
cytoplasm before translocating to the nucleus, where they bind to a transcription
complex at the ERE (estrogen response element) on DNA and modulate gene
transcription. ER in the membrane can associate directly with intracellular kinases
such as MAPKinase or IP3-kinase, or they can associate with mGluR located in the
endoplasmic reticulum. Finally, estradiol itself can directly interact with ion channels,
including voltage-gated calcium channels, ionotropic glutamate receptors, or GABA-A
receptors.
 The classic mechanism is the usual activation of the receptor
by a ligand (hormone), which, together with coregulatory
proteins, somehow changes the expression of individual genes.

The receptor interacts with a complex of other transcription

factors that modulate the effect of the receptor on gene
expression.

Does not touch the genome directly. It realizes itself through a

certain cascade of reactions, the result of which is a change in
cellular function in the form of opening/closing of ion channels,
changes in the concentration of NO in the cell. This model mediates
"quick reactions". It is assumed that ER directly associated with the
cell membrane and not freely floating in the cytoplasm may
participate in this; there are also hypotheses that these are non-
estrogen receptors at all (although they are activated by estradiol).

It does not involve the participation of a specific hormone. Any

highly active substance (for example, growth factor - GF-grows
factor) binds to membrane receptors; it causes a cascade of various
reactions, the activation of protein kinases, which, interacting with
estrogen receptors, phosphorylate it; although there are
hypotheses that protein kinases interact not with the ER, but with
coregulatory proteins
 Feminization, masculinization and
defeminization - gender differentiation of
Masculinization behavior.
Testosterone, estradiol Masculinization is an orchestrated process
mediated by a combination of androgens and
estrogens that results in the formation of an
adult brain that is activated by steroids to
lower the threshold for male sexual behavior.
Feminization
Feminization occurs in the absence of gonadal
without steroids steroid secretion during the sensitive period,
resulting in the formation of an adult brain
that is activated by steroids to lower the
threshold for female sexual behavior.
Defeminization is also a steroid-mediated
Defiminization organizational event that removes or inhibits
Testosterone, estradiol the neural substrate of feminization such that
the threshold for active expression of female
sexual behavior is greatly increased in
adulthood.
 In males, steroid hormone control of the GnRH
neuron is altered so that only the negative feedback
effects of sex steroids are realized, so LH release is
pulsatile but continuous, leading to increased sex steroid
levels and sustained gamete production. In women, the
control of LH release is under both positive and negative
feedback control by estradiol, resulting in changes in the
periodicity of LH release and the final LH surge
required for ovulation
 List of genes activated by estrogens.
Genes have two properties. First, estrogens
(E), binding to estrogen receptors (ER),
increase the expression level of their genes
(except for the example below). Second,
these gene products contribute to certain
aspects of female reproductive behavior
 Conclusions
Evidence suggests that gonadal steroid hormones have a
powerful role in promoting sexual behavior in both men and
women. Men need testosterone and estrogen, while women
need estrogen plus progesterone. The medial preoptic area and
the ventral hypothalamus are the main brain regions involved
in the modulation of sexual behavior. Androgens, estrogens,
and progestins affect the genome, changing the synthesis of
new proteins in the brain that are thought to be responsible for
changes in sexual behavior. However, the non-genomic effect of
gonadal hormones is becoming increasingly evident. Research
in animal models has been instrumental in advancing our
understanding of human problems such as androgen
insensitivity, hormone replacement therapy, and the treatment
of hormone-responsive responses in cancer patients.