The nonapeptide hormones arginine vasopressin (AVP) and oxytocin are synthesized in the supraoptic and
paraventricular nuclei of the hypothalamus together with their respective 'carrier' proteins, the neurophysins.
Just before the onset of labor, uterine muscle becomes exceedingly sensitive to oxytocin, for which it is a primary target
tissue, because of a dramatic increase in the number of oxytocin receptors.
NCBI Summary:
There are two proteins encoded by this gene, oxytocin and neurophysin I. Oxytocin is posterior pituitary hormone which is synthesized as an inactive precursor in the hypothalamus along with its carrier protein neurophysin I. Together with neurophysin, it is packaged into neurosecretory vesicles and transported axonally to the nerve endings in the neurohypophysis, where it is either stored or secreted into the bloodstream. The precursor seems to be activated while it is being transported along the axon to the posterior pituitary. This hormone contracts smooth muscle during parturition and lactation. It is also involved in cognition, tolerance, adaptation and complex sexual and maternal behaviour, as well as in the regulation of water excretion and cardiovascular functions.
The Functional Role of Oxytocin in the Induction of Oocyte Meiotic Resumption in Cattle. De Cesaro M et al. The aim of the present study was to examine the role of oxytocin (OT) in the progesterone (P4) and prostaglandins (PGs) pathway to induce oocyte meiotic resumption. Cumulus-oocyte complexes were co-cultured with follicular hemisections for 15h to determine the effects of different doses of OT or atosiban (ATO; oxytocin receptor antagonist) on oocyte meiotic resumption. In another experiment, we examined the effect of the interaction between P4, OT and PGs on the regulatory cascade of the oocyte meiotic resumption. Oxytocin at 1m was effective in inducing meiotic resumption in oocytes co-cultured with follicular cells (84.0%), not differing from the positive control group (74.4%). Atosiban inhibited in a dose-dependent manner the positive effect of OT on the meiotic resumption (27.6% metaphase I with 10m of ATO, which did not differ from the 25.5% of the negative control group). Furthermore, a third experiment showed that P4 was able to induce oocyte meiotic resumption, which was inhibited by ATO. However, the OT positive effect was not blocked by mifepristone (P4 antagonist), but was inhibited by indomethacin (a non-selective PTGS2 inhibitor). Collectively, these data suggest a sequential role of P4, OT and PGs in the induction of oocyte meiotic resumption.
Khan-Dawood FS reviewed oxytocin in intercellular communication in the corpus luteum.
The synthesis of oxytocin and the oxytocin receptor
is influenced by the gonadotropins and locally produced prostaglandins. Oxytocin stimulates estradiol synthesis, which may affect the expression of the gap-junction protein connexin-43, allowing interaction
between the large cells and small cells of the corpus luteum. With the ubiquitous presence of oxytocin
and its receptor, and the presence of gap junctions in the corpora lutea of numerous species, it is
concluded that oxytocin is involved in not only paracrine/autocrine interaction but also may be of
significant importance in intercellular crosstalk in the corpus luteum.
Wuttke W, et al. reviewed luteotropic and luteolytic effects of oxytocin in the porcine corpus luteum.
Wathes DC, et al. reviewed the control of synthesis and secretion of ovarian oxytocin in ruminants.
Mayerhofer A, et al. reported the effect of oxytocin on free intracellular Ca2+ levels and progesterone release by human
granulosa-lutein cells.
Fortune JE et al reported oxytocin gene expression and action in bovine preovulatory
follicles.
Both OT content of granulosa cells and their ability to secrete OT in culture increased
dramatically when follicles were obtained after the gonadotropin surge (LH surge) that triggers
ovulation. These changes were correlated with increased levels of messenger RNA (mRNA) for OT in
granulosa cells obtained after vs. before the LH surge. Estradiol, at concentrations found in follicular fluid of
preovulatory follicles before the LH surge, inhibited OT secretion in vitro, whereas concentrations found
in follicular fluid after the LH surge were not inhibitory. Progesterone, at physiological concentrations,
stimulated OT secretion in vitro.
Chandrasekher YA, et al. reported effects of oxytocin on steroidogenesis by bovine theca and granulosa cells.
Expression regulated by
LH, Steroids, Eicosanoids
Comment
Fuchs AR reviewed that
(1) Oxytocin is synthesized in the luteal cells of all species so far studied, including the human.
Vasopressin is also synthesized, but at a much lower rate. (2) The oxytocin-neurophysin gene is
expressed in granulosa cells and granulosa-derived luteal cells but not in theca cells. Ovulation or
spontaneous luteinization initiates the gene expression which peaks in the early luteal phase and ceases around mid-cycle. (3) Luteal oxytocin concentrations rise with considerable delay after the peak of
specific mRNA and reach maximal levels around mid-cycle. Oxytocin concentrations fall to low levels
in the late luteal phase and in pregnancy. (4) Thecal tissue produces substances such as catecholamines
and ascorbic acid that stimulate oxytocin secretion in granulosa cells. The adrenergic innervation of
thecal tissue provides a source of catecholamines and may therefore serve a modulatory function in
ovarian oxytocin secretion. (5) Oxytocin has little or no direct effect on luteal progesterone production.
(6) Oxytocin inhibits LH-stimulated prostacyclin production in luteal cells of cows. Oxytocin may induce
the release of PGF-2 alpha or lipo-oxygenase products from the ovary but this has not yet been
documented. (7) PGF-2 alpha releases oxytocin from the ovary but does not turn off its synthesis. (8) The
concept that ovarian oxytocin participates in the luteolytic process is gaining acceptance. In some species
(sheep, goat) ovarian oxytocin acts as a hormone causing PGF-2 alpha release from the uterus. In others
it acts in a paracrine or autocrine fashion on ovarian prostanoid production (cow, possibly primates).
Einspanier A et al reported that local oxytocin (OT) system is part of the luteinization process in the
preovulatory follicle of the marmoset monkey.
Before the
endogenous LH increase, OT immunoreactivity was detectable at low levels in most antral follicles,
where its presence was confined to antral granulosa cell (GC) layers. In contrast, immunoreactivity for
the OT receptor (OTR) was localized primarily in the basal GC layer. After application of exogenous
hCG, there was a marked enhancement in both the staining intensity and the number of cells positive for
OT and the OTR in all GC layers of antral follicles, especially in the preovulatory follicle. Secretion of authentic OT was demonstrated from
cultured GC obtained before the LH surge, with highest amounts in cells cultured from preovulatory as
opposed to smaller antral follicles. OT production could be stimulated by the application of hCG to the
GC cultured from preovulatory follicles, whereas the gonadotropin was without effect on GC from small
follicles. FSH had no effect on OT production by GC from either follicle type. Application of OT to the
cultures caused an increase in progesterone production by GC from large preovulatory follicles but was
without effect on steroidogenesis by cells from small antral follicles. These results describing the
presence and distribution of OT and OTR and their modulation by hCG, as well as the luteotrophic effect
of OT in cultured GC from preovulatory follicles, implicate OT as a paracrine mediator in the
luteinization process in the primate ovary.
Voss AK, et al. reported that estradiol-17 beta has a biphasic effect on oxytocin secretion by bovine granulosa cells.
Voss AK, et al. reported that oxytocin/neurophysin-I messenger ribonucleic acid in bovine granulosa cells increases after the
luteinizing hormone (LH) surge and is stimulated by LH in vitro.
Meidan R, et al. reported the biosynthesis and release of oxytocin by granulosa cells derived from preovulatory bovine follicles and
effects of forskolin and insulin-like growth factor-I.
Ovarian localization
Granulosa, Luteal cells, Large luteal cells
Comment
Furuya K et al reported the expression of
oxytocin and oxytocin receptor in cumulus/luteal cells and the
effect of oxytocin on embryogenesis in fertilized oocytes.
Cumulus cells
with mature oocytes were obtained from experimental and clinical in vitro fertilization-embryo transfer
(IVF-ET) programs. OT and OTR gene expression was analyzed with reverse transcriptase-polymerase
chain reaction (RT-PCR) and RT-PCR/single strand conformation polymorphism (SSCP). OT gene
expression was detected in mouse and human cumulus cells. Furthermore, OTR
gene expression was demonstrated in human cumulus cells, and a weak positive signal was
observed in human oocytes. Immunocytochemical staining of OTR was detected in human
cumulus cells. The rate of mouse blastocyst development was significantly higher in the group cultured
with OT than that without OT.
Berndtson AK, et al. reported differential effects of oxytocin on steroid production by bovine granulosa cells.Their findings suggest that: (1) OT plays an autocrine
role in regulating the follicular luteal phase shift in steroidogenesis by both increasing progesterone and
inhibiting estradiol production and (2) the differential effects of OT on steroid production are not
mediated primarily by effects on levels of mRNA for steroidogenic enzymes.
Follicle stages
Antral, Preovulatory, Corpus luteum
Comment
Shaw DW et al reported in vivo oxytocin release from microdialyzed bovine corpora
lutea during spontaneous and prostaglandin-induced regression
Although robust luteal oxytocin release was observed
after treatment with a pharmacological dose of PCF2 alpha, the lack of
detectable oxytocin secretion during spontaneous luteolysis suggests that the
contribution of luteal oxytocin in the cow may be less than that proposed for
the ewe.
Phenotypes
Mutations
1 mutations
Species: mouse
Mutation name: None
type: null mutation fertility: fertile Comment:Young WS 3rd, et al 1996. reported that deficiency in mouse oxytocin prevents milk ejection, but not fertility or parturition.