The physiology of ovarian oxytocin

1999 ◽  
Vol 7 (1) ◽  
pp. 11-25 ◽  
Author(s):  
Richard Ivell

The notion of an oxytocic principle residing within the ovary is not new. In as early as 1910, Ott and Scott showed that an extract of bovine corpus luteum could induce milk letdown and uterine contraction. However, it took a further 70 years before the identification of this principle with the nonapeptide hormone oxytocin (OT) was made at the peptide and mRNA levels. This was followed by the identification of the peptide in ovarian tissues and ovarian venous blood from a wide variety of species, including humans, monkeys, pigs and ruminants (reviewed in 7, 8). For the majority of non-ruminant species the levels of expression of the peptide and its specific mRNA are relatively low, implying that whatever function the ovarian hormone has in these species, it is most likely to be at the local, paracrine level. Ruminants are an exception. Cows and sheep both produce very high levels of OT and OT-mRNA – the latter attaining concentrations of approximately 1% of all transcripts – within the corpus luteum of the early oestrous cycle. In ruminants, evolution has culminated in a systemic link between ovarian OT production and OT receptors in the endometrium of the uterus, inducing there the production of prostaglandin-F2∞ (PGF2∞) which completes a positive feedback loop to the ovary by stimulating further OT release (reviewed in 10). It is important to note, however, that natural selection can only act on a preexisting system. In this case, it has developed a systemic endocrine pathway in ruminants from a local ovarian OT system present probably in all mammals. There is even evidence for OT-related peptides, such as mesotocin and vasotocin, within the ovaries of marsupials and chicken, though their function is not known.

Reproduction ◽  
2016 ◽  
Vol 151 (4) ◽  
pp. 391-399 ◽  
Author(s):  
J Lüttgenau ◽  
K Herzog ◽  
K Strüve ◽  
S Latter ◽  
A Boos ◽  
...  

When given intravenously (iv), lipopolysaccharide (LPS) transiently suppresses the structure and function of the bovine corpus luteum (CL). This is associated with increased release of prostaglandin (PG) F2α metabolite. The underlying regulatory mechanisms of this process remain, however, obscure. Therefore, the aims of this study were: i) to investigate the expression of the LPS receptor toll-like receptor 4 (TLR4) and 2 (TLR2) in the bovine CL during early, mid- and late luteal phases; and ii) to further dissect the mechanisms of LPS-mediated suppression of luteal function. As revealed by semi-quantitative qPCR and immunohistochemistry, both receptors were detectable throughout the luteal lifespan. Their mRNA levels increased from the early toward the mid-luteal phase; no further changes were observed thereafter. The TLR4 protein seemed more highly represented than TLR2. The cellular localization of TLRs was in blood vessels; weaker signals were observed in luteal cells. Additionally, cows were treated either with LPS (iv, 0.5 μg/kg BW) or with saline on Day 10 after ovulation. Samples were collected 1200 h after treatment and on Day 10 of the respective subsequent (untreated) cycle. The mRNA expression of several possible regulatory factors was investigated, revealing the suppression of PGF2α receptor (PTGFR), STAR protein and 3β-hydroxysteroid dehydrogenase, compared with controls and subsequent cycles. The expression of TLR2 and TLR4, interleukin 1α (IL1A) and 1β (IL1B) and of PGF2α and PGE2 synthases (HSD20A and mPTGES respectively) was increased. The results demonstrate the presence of TLR2 and TLR4 in the bovine CL, and implicate their possible involvement in the deleterious effects of LPS on its function.


Reproduction ◽  
2002 ◽  
pp. 429-434 ◽  
Author(s):  
C Veitch ◽  
L Brown ◽  
C Sernia ◽  
RT Gemmell

Maturation of the fetal pituitary and adrenal glands allows the secretion of cortisol, which in turn leads to an increase in prostaglandin and mesotocin production. The production of prostaglandin and mesotocin results in an increase in uterine contractions and initiates birth in marsupials. The major metabolite of PGF(2alpha), 13,14-dihydro-15-keto-prostaglandin F(2alpha) (PGFM), has been found in the plasma of the possum at the time of birth and administration of PGF(2alpha) to female possums induced the adoption of the birth position. Evidence that mesotocin is an integral hormone of birth in the tammar wallaby indicates that both PGF(2alpha) and mesotocin or oxytocin are required for marsupial birth. The presence of PGF(2alpha) receptors in the uterus and corpus luteum of the possum, and the in vitro uterine responsiveness to PGF(2alpha) or oxytocin, were examined. PGF(2alpha) receptors were not observed in possum uteri and the inability of PGF(2alpha) to cause contractions indicates that PGF(2alpha) is not involved directly in contraction of the uterus at parturition. The presence of oxytocin and mesotocin receptors in the uterus of possoms and the ability of oxytocin to induce uterine contraction in vitro supports the view that mesotocin is required for expulsion of the young from the uterus. Low numbers of PGF(2alpha) receptors were found in the possum corpus luteum at birth, indicating an involvement of PGF(2alpha) in regression of the corpus luteum.


2022 ◽  
Vol 8 ◽  
Author(s):  
Agnieszka W. Jonczyk ◽  
Katarzyna K. Piotrowska-Tomala ◽  
Dariusz J. Skarzynski

We investigated the effects of different doses of dinoprost injected directly into the bovine corpus luteum (CL) on (i) concentrations of progesterone (P4) and oxytocin (OT) in peripheral blood and (ii) mRNA levels of steroidogenic acute regulatory protein (STAR), cytochrome P450 family 11 subfamily A member 1 (P450scc), hydroxy-delta-5-steroid dehydrogenase, 3 β- and steroid delta-isomerase 1 (HSD3B), and receptor-interacting protein kinases 1 and 3 (RIPK1, RIPK3) in CL tissue. Moreover, we examined the effects of dinoprost, injected intra-CL or administered intramuscularly (IM), on CL secretory function and on indicators of CL vascular network status: luteal tissue area (LTA), CL blood flow (CLBF), and the CLBF:LTA ratio (Adj. CLBF), in cows at the early and mid-luteal phases. In the Experiment 1, cows (day 10 of the cycle) were allocated to (i) an intra-CL injection of saline (control; n = 3); (ii) an intra-CL injection of dinoprost (1.25 mg; 2.5 mg, or 5 mg; n = 3 for each dose); (iii) an IM administration of saline (control; n = 3); or (iv) an IM administration of dinoprost (25 mg; positive control; n = 3). Concentrations of OT and P4 were measured in plasma samples. The mRNA expression of steroidogenesis- or necroptosis-related factors was determined in CL tissue 4 h after treatments. In Experiment 2, cows on day 4 (n = 12) or day 10 (n = 12) were allocated to (i) an intra-CL injection of dinoprost (2.5 mg/0.5 ml; n = 6), or (ii) IM administration of dinoprost (25 mg/5 ml; n = 6). Concentrations of P4 were measured in plasma samples. Luteal tissue area, CLBF, and Adj. CLBF were assessed based on color Doppler ultrasonography. An intra-CL injection of dinoprost increased OT and decreased P4 levels in the jugular vein (JV) in a dose-dependent manner in cows at the mid-luteal phase. Increased CLBF and Adj. CLBF, accompanied by reduced P4 levels, were observed 2 h after intra-CL dinoprost injection in middle-stage CL. Decreased STAR and increased RIPK1 and RIPK3 mRNA levels confirmed that 2.5 mg dinoprost injected directly into CL is the minimum dose that induces luteolytic cascade. Injection of dinoprost directly into the CL (at a dosage lower than recommended for peripheral application) results in a pattern similar to IM dinoprost administration.


Endocrinology ◽  
1996 ◽  
Vol 137 (12) ◽  
pp. 5191-5196 ◽  
Author(s):  
E Girsh ◽  
W Wang ◽  
R Mamluk ◽  
F Arditi ◽  
A Friedman ◽  
...  

2001 ◽  
Vol 49 (1) ◽  
pp. 39-51 ◽  
Author(s):  
Grażyna Miszkiel ◽  
J. Kotwica

The present studies were conducted: (1) to determine which β-adrenoceptor subtypes are involved in progesterone and oxytocin (OT) secretion, (2) to examine whether noradrenaline (NA) acts directly on the cytochrome P-450scc and 3β-hydroxysteroid dehydrogenase (3β-HSD), and (3) to study the effect of prostaglandin F2α, (PGF2α) on NA-stimulated steroidogenesis in luteal cells. The effect of NA on progesterone secretion from luteal slices of heifers on days 8–12 of the oestrous cycle was blocked by both atenolol (β1-antagonist) and ICI 118.551 hydrochloride (β2-antagonist). OT secretion was blocked only after treatment with ICI 118.551 hydrochloride (P < 0.05). Dobutamine (10−4−10−6), a selective β1 agonist and salbutamol (10−4−10−6), a selective β2 agonist, both increased progesterone production (P < 0.01) with an efficiency comparable to that produced by NA (P < 0.01). The increase of OT content in luteal slices was observed only after treatment with salbutamol at the dose of 10−5M (P < 0.01). Dobutamine had no effect on OT production at any dose. A stimulatory effect of NA on cytochrome P-450scc activity (P < 0.05) was demonstrated using 25-hydroxycholesterol as substrate. 3β-HSD activity also increased following NA (P < 0.01) or pregnenolone (P < 0.05) and in tissue treated with pregnenolone together with NA (P < 0.01). PGF decreased progesterone synthesis (P < 0.05) and 3β-HSD activity (P < 0.01) in tissue treated with NA. We conclude that NA stimulates progesterone secretion by luteal β1- and β2-adrenoceptors, while OT secretion is probably mediated only via the β2-receptor. NA also increases cytochrome P-450scc and 3β-HSD activity. PGF inhibits the luteotropic effect of NA on the luteal tissue.


2004 ◽  
Vol 82 (6) ◽  
pp. 363-371 ◽  
Author(s):  
R M Narayansingh ◽  
M Senchyna ◽  
M M Vijayan ◽  
J C Carlson

In this study we examined the mechanism of corpus luteum (CL) regression by measuring changes in expression of prostaglandin G/H synthase-1 (PGHS-1) and -2 (PGHS-2) in day 4 CL and inducible heat shock protein 70 (HSP-70) in day 4 and day 9 CL of immature superovulated rats. The rats were superovulated and treated with 500 µg of prostaglandin F2α (PGF2α) on day 4 or day 9 after CL formation. Ovaries and serial blood samples were removed during the 24-hour period following treatment. Plasma progesterone was determined by radioimmunoassay while mRNA abundance and protein expression were assessed by semiquantitative RT-PCR and immunoblot analysis, respectively. One hour after PGF2α, both day 4 and day 9 rats exhibited a significant decrease in progesterone secretion; however, there was a greater decrease in day 9 rats. In ovarian samples removed on day 4, there was a significant increase in mRNA for PGHS-2 at 1 hour after PGF2α. PGHS-1 mRNA content remained unchanged. Immunoblot analyses showed an increase in PGHS-2 protein expression only at 8 h. There were no changes in PGHS-1 protein expression. In day 9 rats, ovarian HSP-70 protein levels increased by 50% after PGF2α injection; however, on day 4 there was no change in expression of this protein over the sampling period. These results suggest that expression of PGHS-2 may be involved in inhibiting progesterone production and that expression of HSP-70 may be required for complete CL regression in the rat.Key words: rat, prostaglandin F2α, corpus luteum, prostaglandin G/H synthase, heat shock protein-70.


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