Gonadotropin surge-attenuating factor (GnSAF) is a
nonsteroidal A nonsteroidal compound is a drug that is not a steroid nor a steroid derivative. Nonsteroidal anti-inflammatory drugs (NSAIDs) are distinguished from corticosteroids as a class of anti-inflammatory agents.
List of nonsteroidal steroid receptor mo ...
ovarian hormone produced by the
granulosa cells
A granulosa cell or follicular cell is a somatic cell of the sex cord that is closely associated with the developing female gamete (called an oocyte or egg) in the ovary of mammals.
Structure and function
In the primordial ovarian follicle, and ...
of small
antral ovarian follicles in females.
GnSAF is involved in regulating the secretion of
luteinizing hormone
Luteinizing hormone (LH, also known as luteinising hormone, lutropin and sometimes lutrophin) is a hormone produced by gonadotropic cells in the anterior pituitary gland. The production of LH is regulated by gonadotropin-releasing hormone (G ...
(LH) from the
anterior pituitary
The anterior pituitary (also called the adenohypophysis or pars anterior) is a major Organ (anatomy), organ of the endocrine system. The anterior pituitary is the glandular, Anatomical terms of location#Usage in human anatomy, anterior lobe that t ...
and the
ovarian cycle
The menstrual cycle is a series of natural changes in hormone production and the structures of the uterus and ovaries of the female reproductive system that makes pregnancy possible. The ovarian cycle controls the production and release of eg ...
.
During the early to mid-
follicular phase
The follicular phase, also known as the preovulatory phase or proliferative phase, is the phase of the estrous cycle (or, in primates for example, the menstrual cycle) during which follicles in the ovary mature from primary follicle to a full ...
of the ovarian cycle, GnSAF acts on the anterior pituitary to attenuate LH release, limiting the secretion of LH to only basal levels.
At the transition between follicular and
luteal phase
The menstrual cycle is on average 28 days in length. It begins with Menstruation, menses (day 1–7) during the follicular phase (day 1–14), followed by ovulation (day 14) and ending with the luteal phase (day 14–28). While historically, medi ...
, GnSAF bioactivity declines sufficiently to permit LH
secretion
Secretion is the movement of material from one point to another, such as a secreted chemical substance from a cell or gland. In contrast, excretion is the removal of certain substances or waste products from a cell or organism. The classical mec ...
above basal levels, resulting in the mid-cycle
LH surge
Luteinizing hormone (LH, also known as luteinising hormone, lutropin and sometimes lutrophin) is a hormone produced by gonadotropic cells in the anterior pituitary gland. The production of LH is regulated by gonadotropin-releasing hormone (GnR ...
that initiates
ovulation
Ovulation is an important part of the menstrual cycle in female vertebrates where the egg cells are released from the ovaries as part of the ovarian cycle. In female humans ovulation typically occurs near the midpoint in the menstrual cycle and ...
.
In normally ovulating women, the LH surge only occurs when the
oocyte
An oocyte (, oöcyte, or ovocyte) is a female gametocyte or germ cell involved in reproduction. In other words, it is an immature ovum, or egg cell. An oocyte is produced in a female fetus in the ovary during female gametogenesis. The female ger ...
is mature and ready for
extrusion
Extrusion is a process used to create objects of a fixed cross section (geometry), cross-sectional profile by pushing material through a Die (manufacturing), die of the desired cross-section. Its two main advantages over other manufacturing pro ...
.
GnSAF bioactivity is responsible for the synchronised, biphasic nature of LH secretion.
Molecular structure and characteristics
GnSAF is a large molecule consisting of subunits that has the same structure as the
carboxyl
In organic chemistry, a carboxylic acid is an organic acid that contains a carboxyl group () attached to an R-group. The general formula of a carboxylic acid is often written as or , sometimes as with R referring to an organyl group (e.g. ...
terminal fragment of
human serum albumin
Human serum albumin is the serum albumin found in human blood. It is the most abundant protein in human blood plasma; it constitutes about half of serum protein. It is produced in the liver. It is soluble in water, and it is monomeric.
Albumin ...
(HAS).
However, HSA, in its complete form, does not exhibit any GnSAF activity.
The smallest biologically active fraction of GnSAF found in human
follicular fluid
Follicular fluid is a liquid which fills the follicular antrum and surrounds the oocyte in an ovarian follicle. This fluid is rich in hyaluronic acid, and is used in a modified intracytoplasmic sperm injection (ICSI) called physiological ICSI (P ...
is a
peptide
Peptides are short chains of amino acids linked by peptide bonds. A polypeptide is a longer, continuous, unbranched peptide chain. Polypeptides that have a molecular mass of 10,000 Da or more are called proteins. Chains of fewer than twenty am ...
of
molecular mass
The molecular mass () is the mass of a given molecule, often expressed in units of daltons (Da). Different molecules of the same compound may have different molecular masses because they contain different isotopes of an element. The derived quan ...
12.5 kDA.
The activity of other subunits has not yet been clarified, but it has been confirmed that more than one
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
contributes to the attenuating effect of GnSAF.
Since GnSAF is found in very low concentrations in the human
follicular fluid
Follicular fluid is a liquid which fills the follicular antrum and surrounds the oocyte in an ovarian follicle. This fluid is rich in hyaluronic acid, and is used in a modified intracytoplasmic sperm injection (ICSI) called physiological ICSI (P ...
, GnSAF in women has been difficult to isolate, sequence and conclusively characterise.
Synthesis of GnSAF
GnSAF is produced in the
granulosa cells
A granulosa cell or follicular cell is a somatic cell of the sex cord that is closely associated with the developing female gamete (called an oocyte or egg) in the ovary of mammals.
Structure and function
In the primordial ovarian follicle, and ...
of the small sized
antral follicles
An antral or secondary follicle, also known as Graafian follicle and tertiary follicle, is an ovarian follicle during a certain latter stage of folliculogenesis.
Definitions differ in where the shift into an antral follicle occurs in the stag ...
, which have the highest concentration of GnSAF.
Concentrations of GnSAF bioactivity is inversely proportional to
follicle size.
Upon synthesis, GnSAF is released into
peripheral circulation.
Follicle-stimulating hormone
Follicle-stimulating hormone (FSH) is a gonadotropin, a glycoprotein polypeptide hormone. FSH is synthesized and secreted by the gonadotropic cells of the anterior pituitary gland and regulates the development, growth, puberty, pubertal maturat ...
(FSH) from the
anterior pituitary
The anterior pituitary (also called the adenohypophysis or pars anterior) is a major Organ (anatomy), organ of the endocrine system. The anterior pituitary is the glandular, Anatomical terms of location#Usage in human anatomy, anterior lobe that t ...
stimulates and prolongs GnSAF
biosynthesis
Biosynthesis, i.e., chemical synthesis occurring in biological contexts, is a term most often referring to multi-step, enzyme-Catalysis, catalyzed processes where chemical substances absorbed as nutrients (or previously converted through biosynthe ...
in growing small
antral follicles
An antral or secondary follicle, also known as Graafian follicle and tertiary follicle, is an ovarian follicle during a certain latter stage of folliculogenesis.
Definitions differ in where the shift into an antral follicle occurs in the stag ...
in the
ovary
The ovary () is a gonad in the female reproductive system that produces ova; when released, an ovum travels through the fallopian tube/ oviduct into the uterus. There is an ovary on the left and the right side of the body. The ovaries are end ...
.
FSH induces
expression and
transcription
Transcription refers to the process of converting sounds (voice, music etc.) into letters or musical notes, or producing a copy of something in another medium, including:
Genetics
* Transcription (biology), the copying of DNA into RNA, often th ...
of
exons
An exon is any part of a gene that will form a part of the final mature RNA produced by that gene after introns have been removed by RNA splicing. The term ''exon'' refers to both the DNA sequence within a gene and to the corresponding sequence i ...
12 and 13 of the HSA
gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
found in
granulosa cells
A granulosa cell or follicular cell is a somatic cell of the sex cord that is closely associated with the developing female gamete (called an oocyte or egg) in the ovary of mammals.
Structure and function
In the primordial ovarian follicle, and ...
. During the early and mid-follicular phase, FSH is secreted to promote growth and proliferation of the granulosa cells, which increases GnSAF concentrations.
Once the
dominant ovarian follicle has been selected at mid-follicular phase, the
non-dominant follicles undergo
atresia
Atresia is a condition in which an orifice or passage in the body is (usually abnormally) closed or absent.
Types Anotia
Anotia is characterized by the complete absence of the ear and is extremely rare. This condition may affect one or both ...
.
Without the presence of small follicles during the late follicular phase, GnSAF concentrations steadily decline to its lowest levels observable in the
ovarian cycle
The menstrual cycle is a series of natural changes in hormone production and the structures of the uterus and ovaries of the female reproductive system that makes pregnancy possible. The ovarian cycle controls the production and release of eg ...
.
Additionally, the rate of GnSAF biosynthesis by the
granulosa cells
A granulosa cell or follicular cell is a somatic cell of the sex cord that is closely associated with the developing female gamete (called an oocyte or egg) in the ovary of mammals.
Structure and function
In the primordial ovarian follicle, and ...
of the remaining dominant follicle decreases as the follicle approaches
maturation.
During the transition between
luteal phase
The menstrual cycle is on average 28 days in length. It begins with Menstruation, menses (day 1–7) during the follicular phase (day 1–14), followed by ovulation (day 14) and ending with the luteal phase (day 14–28). While historically, medi ...
and follicular phase, GnSAF gradually increases from the late luteal phase and onwards due to the recruitment of
follicles and concomitant rise of FSH.
The time-course production of GnSAF depends on the
serum FSH concentrations.
Higher serum concentrations of FSH increases the potency of the attenuating effects of GnSAF on release of LH.
However, there is a limit to how much FSH can stimulate GnSAF production: FSH doses above 450 IU do not elicit any more increases in GnSAF bioactivity.
Function
GnSAF antagonises the
positive feedback
Positive feedback (exacerbating feedback, self-reinforcing feedback) is a process that occurs in a feedback loop where the outcome of a process reinforces the inciting process to build momentum. As such, these forces can exacerbate the effects ...
effects of
estradiol
Estradiol (E2), also called oestrogen, oestradiol, is an estrogen steroid hormone and the major female sex hormone. It is involved in the regulation of female reproductive cycles such as estrous and menstrual cycles. Estradiol is responsible ...
on
GnRH
Gonadotropin-releasing hormone (GnRH) is a releasing hormone responsible for the release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the anterior pituitary. GnRH is a tropic peptide hormone synthesized and released ...
-induced LH release during the follicular phase.
GnSAF inhibits the stimulatory role of estradiol in increasing GnRH-induced
''de novo'' synthesis of
GnRH receptors in the pituitary.
GnRH receptor
mRNA
In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of Protein biosynthesis, synthesizing a protein.
mRNA is ...
levels are low in the presence of high GnSAF bioactivity, which limits the availability of
binding sites
In biochemistry and molecular biology, a binding site is a region on a macromolecule such as a protein that binds to another molecule with specificity. The binding partner of the macromolecule is often referred to as a ligand. Ligands may includ ...
for GnRH at the pituitary and decreased pituitary sensitivity to GnRH.
The moderated GnRH
pulse amplitude and frequency is sufficient for maintaining low
blood
Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells.
Blood is com ...
concentrations of LH and protects against premature LH surges and LH
hypersecretion.
GnSAF also inhibits LH synthesis after the transcription stage and limits stored LH in the pituitary. Whilst the pulse amplitude of LH is reduced by GnSAF,
constitutive production of LH is unaffected by GnSAF.
Effects on the ovarian cycle in women
Follicular phase
GnSAF prevents a pre-ovulatory surge in LH during this time, allowing sufficient time for the
dominant follicle to mature before
ovulation
Ovulation is an important part of the menstrual cycle in female vertebrates where the egg cells are released from the ovaries as part of the ovarian cycle. In female humans ovulation typically occurs near the midpoint in the menstrual cycle and ...
.
At the start of the follicular phase, high serum FSH concentrations stimulate the development and proliferation of the granulosa cells of the small antral follicles, resulting in a steady increase in GnSAF
biosynthesis
Biosynthesis, i.e., chemical synthesis occurring in biological contexts, is a term most often referring to multi-step, enzyme-Catalysis, catalyzed processes where chemical substances absorbed as nutrients (or previously converted through biosynthe ...
.
The relatively high GnSAF bioactivity dampens the response of the
pituitary gland
The pituitary gland or hypophysis is an endocrine gland in vertebrates. In humans, the pituitary gland is located at the base of the human brain, brain, protruding off the bottom of the hypothalamus. The pituitary gland and the hypothalamus contr ...
to GnRH by antagonising the sensitising effects of
estradiol
Estradiol (E2), also called oestrogen, oestradiol, is an estrogen steroid hormone and the major female sex hormone. It is involved in the regulation of female reproductive cycles such as estrous and menstrual cycles. Estradiol is responsible ...
on the pituitary gland.
The GnRH pulse, in the presence of GnSAF, is not frequent or potent enough to stimulate LH secretion from the anterior pituitary above basal levels.

The tonic FSH and LH pulses sufficiently stimulate the
theca cells of the follicle to produce
androgen
An androgen (from Greek ''andr-'', the stem of the word meaning ) is any natural or synthetic steroid hormone that regulates the development and maintenance of male characteristics in vertebrates by binding to androgen receptors. This includes ...
substrates for granulosa cell
aromatase
Aromatase (), also called estrogen synthetase or estrogen synthase, is an enzyme responsible for a key step in the biosynthesis of estrogens. It is CYP19A1, a member of the cytochrome P450 superfamily, which are monooxygenases that catalyze man ...
and induces
cytochrome P450
Cytochromes P450 (P450s or CYPs) are a Protein superfamily, superfamily of enzymes containing heme as a cofactor (biochemistry), cofactor that mostly, but not exclusively, function as monooxygenases. However, they are not omnipresent; for examp ...
enzymes
An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as pro ...
that can produce
progesterone
Progesterone (; P4) is an endogenous steroid and progestogen sex hormone involved in the menstrual cycle, pregnancy, and embryogenesis of humans and other species. It belongs to a group of steroid hormones called the progestogens and is the ma ...
later in the
luteal phase
The menstrual cycle is on average 28 days in length. It begins with Menstruation, menses (day 1–7) during the follicular phase (day 1–14), followed by ovulation (day 14) and ending with the luteal phase (day 14–28). While historically, medi ...
.
Androgen substrates from the theca cells are used by the enlarging granulosa cells to produce more
estradiol
Estradiol (E2), also called oestrogen, oestradiol, is an estrogen steroid hormone and the major female sex hormone. It is involved in the regulation of female reproductive cycles such as estrous and menstrual cycles. Estradiol is responsible ...
.
At mid-follicular phase, GnSAF bioactivity gradually declines as the dominant follicle is established and the small subordinate follicles undergo
atresia
Atresia is a condition in which an orifice or passage in the body is (usually abnormally) closed or absent.
Types Anotia
Anotia is characterized by the complete absence of the ear and is extremely rare. This condition may affect one or both ...
.
The development of the dominant follicle and regression of small non-dominant follicles is supported by increasing
estradiol
Estradiol (E2), also called oestrogen, oestradiol, is an estrogen steroid hormone and the major female sex hormone. It is involved in the regulation of female reproductive cycles such as estrous and menstrual cycles. Estradiol is responsible ...
secretion.
Towards the end of the follicular phase, GnSAF bioactivity is at its lowest due to the absence of small antral follicles.
Estradiol secretion from the dominant follicle exponentially increases and exceeds a threshold which switches estradiol feedback on GnRH pulse frequency from
negative to
positive
Positive is a property of positivity and may refer to:
Mathematics and science
* Positive formula, a logical formula not containing negation
* Positive number, a number that is greater than 0
* Plus sign, the sign "+" used to indicate a positi ...
.
Pituitary sensitivity to GnRH is restored.
Mid-cycle
The absence of GnSAF lowers the threshold for GnRH pulse frequency and amplitude required to stimulate the
anterior pituitary
The anterior pituitary (also called the adenohypophysis or pars anterior) is a major Organ (anatomy), organ of the endocrine system. The anterior pituitary is the glandular, Anatomical terms of location#Usage in human anatomy, anterior lobe that t ...
to secrete LH.
Concurrently, GnRH pulse frequency and amplitude increases, which allows LH secretion significantly higher than basal levels.
The LH secretion most noticeable as a LH surge lasting 48 to 72 hours in the middle of the ovarian cycle.
Meiosis
Meiosis () is a special type of cell division of germ cells in sexually-reproducing organisms that produces the gametes, the sperm or egg cells. It involves two rounds of division that ultimately result in four cells, each with only one c ...
in the dominant follicle resumes and follicle ruptures shortly after the LH surge.
Ovulation
Ovulation is an important part of the menstrual cycle in female vertebrates where the egg cells are released from the ovaries as part of the ovarian cycle. In female humans ovulation typically occurs near the midpoint in the menstrual cycle and ...
can only occur if GnSAF is absent and the mid-cycle LH surge occurs.
Luteal phase
Immediately after the LH surge and subsequent
ovulation
Ovulation is an important part of the menstrual cycle in female vertebrates where the egg cells are released from the ovaries as part of the ovarian cycle. In female humans ovulation typically occurs near the midpoint in the menstrual cycle and ...
,
estradiol
Estradiol (E2), also called oestrogen, oestradiol, is an estrogen steroid hormone and the major female sex hormone. It is involved in the regulation of female reproductive cycles such as estrous and menstrual cycles. Estradiol is responsible ...
concentrations drop and the
corpus luteum
The corpus luteum (Latin for "yellow body"; : corpora lutea) is a temporary endocrine structure in female ovaries involved in the production of relatively high levels of progesterone, and moderate levels of estradiol, and inhibin A. It is the ...
develops.
Towards the end of
luteal phase
The menstrual cycle is on average 28 days in length. It begins with Menstruation, menses (day 1–7) during the follicular phase (day 1–14), followed by ovulation (day 14) and ending with the luteal phase (day 14–28). While historically, medi ...
, GnSAF production in the small antral follicles increases steadily.
FSH does not stimulate GnSAF production in the
corpus luteum
The corpus luteum (Latin for "yellow body"; : corpora lutea) is a temporary endocrine structure in female ovaries involved in the production of relatively high levels of progesterone, and moderate levels of estradiol, and inhibin A. It is the ...
, so GnSAF bioactivity is low after ovulation, until the intercycle rise in FSH occurs.
Relationship between GnRH and GnSAF
GnRH
Gonadotropin-releasing hormone (GnRH) is a releasing hormone responsible for the release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the anterior pituitary. GnRH is a tropic peptide hormone synthesized and released ...
and GnSAF are functionally antagonistic over the control of LH secretion in the
hypothalamic-pituitary axis.
In the presence of GnSAF,
endogenous
Endogeny, in biology, refers to the property of originating or developing from within an organism, tissue, or cell.
For example, ''endogenous substances'', and ''endogenous processes'' are those that originate within a living system (e.g. an ...
pulses of GnRH from the
hypothalamus
The hypothalamus (: hypothalami; ) is a small part of the vertebrate brain that contains a number of nucleus (neuroanatomy), nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrin ...
still persist, in approximately one hour intervals.
Due to this large time interval between consecutive GnRH pulses, GnSAF effectively limits the effects of GnRH on the
anterior pituitary
The anterior pituitary (also called the adenohypophysis or pars anterior) is a major Organ (anatomy), organ of the endocrine system. The anterior pituitary is the glandular, Anatomical terms of location#Usage in human anatomy, anterior lobe that t ...
.
GnSAF acts on the
gonadotropic cells of the pituitary to neutralise the
second messenger pathway responsible for transducing GnRH signalling in the
gonadotropes.
The effectiveness of downstream actions of GnRH, such as
calcium
Calcium is a chemical element; it has symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar to it ...
mobilisation and the
protein kinase C
In cell biology, protein kinase C, commonly abbreviated to PKC (EC 2.7.11.13), is a family of protein kinase enzymes that are involved in controlling the function of other proteins through the phosphorylation of hydroxyl groups of serine and t ...
system, are reduced by GnSAF.
These antagonistic effects of GnSAF on GnRH keeps the
anterior pituitary
The anterior pituitary (also called the adenohypophysis or pars anterior) is a major Organ (anatomy), organ of the endocrine system. The anterior pituitary is the glandular, Anatomical terms of location#Usage in human anatomy, anterior lobe that t ...
in a low responsiveness state, which prevents acute elevations of serum LH concentrations until GnSAF bioactivity declines.
When
estradiol
Estradiol (E2), also called oestrogen, oestradiol, is an estrogen steroid hormone and the major female sex hormone. It is involved in the regulation of female reproductive cycles such as estrous and menstrual cycles. Estradiol is responsible ...
concentrations are high in the
late follicular phase, GnRH pulse frequency and amplitude increases and overrides the
attenuating effects of GnSAF.
Frequent and consecutive
exogenous
In a variety of contexts, exogeny or exogeneity () is the fact of an action or object originating externally. It is the opposite of endogeneity or endogeny, the fact of being influenced from within a system.
Economics
In an economic model, an ...
administration of GnRH at submaximal doses is sufficient in overcoming the neutralizing effects of GnSAF. This is because
estradiol
Estradiol (E2), also called oestrogen, oestradiol, is an estrogen steroid hormone and the major female sex hormone. It is involved in the regulation of female reproductive cycles such as estrous and menstrual cycles. Estradiol is responsible ...
lowers the GnRH pulse frequency and amplitude required to stimulate the
biosynthesis
Biosynthesis, i.e., chemical synthesis occurring in biological contexts, is a term most often referring to multi-step, enzyme-Catalysis, catalyzed processes where chemical substances absorbed as nutrients (or previously converted through biosynthe ...
and
secretion
Secretion is the movement of material from one point to another, such as a secreted chemical substance from a cell or gland. In contrast, excretion is the removal of certain substances or waste products from a cell or organism. The classical mec ...
of LH.
Associated disease states and abnormalities
Abnormal GnSAF bioactivity has been associated with premature surges in LH and LH hypersecretion. Optimal and timely changes in serum LH concentrations are crucial to ensuring the viability of
oocytes
An oocyte (, oöcyte, or ovocyte) is a female gametocyte or germ cell involved in reproduction. In other words, it is an immature ovum, or egg cell. An oocyte is produced in a female fetus in the ovary during female gametogenesis. The female ger ...
and
implantation after
fertilization
Fertilisation or fertilization (see American and British English spelling differences#-ise, -ize (-isation, -ization), spelling differences), also known as generative fertilisation, syngamy and impregnation, is the fusion of gametes to give ...
.
For successful implantation of a
zygote
A zygote (; , ) is a eukaryote, eukaryotic cell (biology), cell formed by a fertilization event between two gametes.
The zygote's genome is a combination of the DNA in each gamete, and contains all of the genetic information of a new individ ...
, the mid-cycle LH surge after the decline of GnSAF and
ovulation
Ovulation is an important part of the menstrual cycle in female vertebrates where the egg cells are released from the ovaries as part of the ovarian cycle. In female humans ovulation typically occurs near the midpoint in the menstrual cycle and ...
must correspond with
uterine
The uterus (from Latin ''uterus'', : uteri or uteruses) or womb () is the organ in the reproductive system of most female mammals, including humans, that accommodates the embryonic and fetal development of one or more fertilized eggs until bir ...
receptivity.
Hypersecretion of LH contributes to cycle disturbance,
infertility
In biology, infertility is the inability of a male and female organism to Sexual reproduction, reproduce. It is usually not the natural state of a healthy organism that has reached sexual maturity, so children who have not undergone puberty, whi ...
and increased chances of
miscarriage
Miscarriage, also known in medical terms as a spontaneous abortion, is an end to pregnancy resulting in the loss and expulsion of an embryo or fetus from the womb before it can fetal viability, survive independently. Miscarriage before 6 weeks ...
.
GnSAF has been implicated in
polycystic ovary syndrome
Polycystic ovary syndrome, or polycystic ovarian syndrome, (PCOS) is the most common endocrine disorder in women of reproductive age. The name is a misnomer, as not all women with this condition develop cysts on their ovaries. The name origin ...
(PCOS), one of the most common
ovarian disorders responsible for causing
anovulatory infertility.
Approximately 40% of women with PCOS display higher GnRH pulse frequency and tonic hypersecretion of LH due to hypersecretion of
androgens
An androgen (from Greek ''andr-'', the stem of the word meaning ) is any natural or synthetic steroid hormone that regulates the development and maintenance of male characteristics in vertebrates by binding to androgen receptors. This includes ...
from the
polycystic ovary.
Androgens
An androgen (from Greek ''andr-'', the stem of the word meaning ) is any natural or synthetic steroid hormone that regulates the development and maintenance of male characteristics in vertebrates by binding to androgen receptors. This includes ...
are readily metabolized to
estradiol
Estradiol (E2), also called oestrogen, oestradiol, is an estrogen steroid hormone and the major female sex hormone. It is involved in the regulation of female reproductive cycles such as estrous and menstrual cycles. Estradiol is responsible ...
in the ovaries.
The supraphysiological concentrations of
estradiol
Estradiol (E2), also called oestrogen, oestradiol, is an estrogen steroid hormone and the major female sex hormone. It is involved in the regulation of female reproductive cycles such as estrous and menstrual cycles. Estradiol is responsible ...
maintains high pituitary responsiveness to GnRH, permitting the hypersecretion of LH.
Superovulation
Controlled ovarian hyperstimulation is a technique used in assisted reproduction involving the use of fertility medications to induce ovulation by multiple ovarian follicles. These multiple follicles can be taken out by oocyte retrieval (egg colle ...
is common in women who take
medications
Medication (also called medicament, medicine, pharmaceutical drug, medicinal product, medicinal drug or simply drug) is a drug used to medical diagnosis, diagnose, cure, treat, or preventive medicine, prevent disease. Drug therapy (pharmaco ...
such as
clomiphene citrate
Clomifene, also known as clomiphene, is a medication used to treat infertility in women who do not ovulate, including those with polycystic ovary syndrome. It is taken by mouth.
Common side effects include pelvic pain and hot flashes. Oth ...
, an anti-estrogenic oral medication used to treat
infertility
In biology, infertility is the inability of a male and female organism to Sexual reproduction, reproduce. It is usually not the natural state of a healthy organism that has reached sexual maturity, so children who have not undergone puberty, whi ...
.
Superovulation is induced in women to increase chances of fertilization and conception in
assisted reproductive techniques.
In naturally superovulating women, the mid-cycle LH surge is significantly lower compared to that of normal ovulating women due to the presence of GnSAF in the late follicular phase fluid.
The high basal GnSAF bioactivity is due to a greater number of small follicles, the site of GnSAF biosynthesis.
Possible uses in medicine
An alternative to using
GnRH analogues in
IVF treatments could be short-term administration of GnSAF.
During IVF, the ovaries are stimulated by raising
estrogen
Estrogen (also spelled oestrogen in British English; see spelling differences) is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three ...
concentrations to supraphysiological levels, which prevents the mid-cycle LH surge.
Premature LH surges are unfavorable during IVF as it is associated with low
oocyte
An oocyte (, oöcyte, or ovocyte) is a female gametocyte or germ cell involved in reproduction. In other words, it is an immature ovum, or egg cell. An oocyte is produced in a female fetus in the ovary during female gametogenesis. The female ger ...
viability and low success rates during IVF treatment.
GnSAF could be used to influence
ovarian hyperstimulation syndrome
Ovarian hyperstimulation syndrome (OHSS) is a medical condition that can occur in some women who take fertility medication to stimulate egg growth, and in other women in sporadic cases. Most cases are mild, but rarely the condition is severe and c ...
.
Using GnSAF would potentially eliminate the need to use
human chorionic gonadotropin
Human chorionic gonadotropin (hCG) is a hormone for the maternal recognition of pregnancy produced by trophoblast cells that are surrounding a growing embryo (syncytiotrophoblast initially), which eventually forms the placenta after implantat ...
.
Administration of GnSAF could also be used to prevent
ovulation
Ovulation is an important part of the menstrual cycle in female vertebrates where the egg cells are released from the ovaries as part of the ovarian cycle. In female humans ovulation typically occurs near the midpoint in the menstrual cycle and ...
and replace exogenously administered
steroids
A steroid is an organic compound with four fused rings (designated A, B, C, and D) arranged in a specific molecular configuration.
Steroids have two principal biological functions: as important components of cell membranes that alter mem ...
that are often perceived as being risky,
or to delay the naturally premature LH surge observed in some hyperstimulated or
infertile
In biology, infertility is the inability of a male and female organism to reproduce. It is usually not the natural state of a healthy organism that has reached sexual maturity, so children who have not undergone puberty, which is the body's sta ...
women.
GnSAF could form part of a
contraceptive drug or in treatments for
infertility
In biology, infertility is the inability of a male and female organism to Sexual reproduction, reproduce. It is usually not the natural state of a healthy organism that has reached sexual maturity, so children who have not undergone puberty, whi ...
that target LH hypersecretion or abnormal ovarian cycles.
References
{{Hormones
Hormones of the ovary