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Biomedical subjects

G Jenkin

Publications and source records attributed to G Jenkin.

At least 37 records · Page 2Linked to original sources

Effect of nitric oxide synthase inhibition on the uterine vasculature of the late-pregnant ewe.

OBJECTIVES: We studied the role of nitric oxide in the maintenance of uterine vascular tone during pregnancy. STUDY DESIGN: Late-pregnant ewes were instrumented with ultrasonographic flow probes on the left and right main uterine arteries. A catheter was passed retrogradely into 1 uterine artery from a tributary. In 14 animals nitric oxide synthase inhibitor (N omega-nitro-L-arginine methyl ester; L-NAME) was infused at 2 or 20 mg/kg during a 1-minute period into either the main left or right uterine artery. RESULTS: The nitric oxide synthase inhibitor (20 mg/kg), infused into 1 uterine artery, significantly decreased uterine blood flow (P <.001) bilaterally, increased (P <.05) mean arterial pressure, and decreased heart rate (P <.05). The compound (when infused at 2 mg/kg) also significantly (P <.05) decreased uterine blood flow in the artery ipsilateral to, but not contralateral to, the infusion, with no change in mean arterial pressure and a decrease (P <.05) in heart rate. CONCLUSION: During ovine pregnancy, endogenous nitric oxide production contributes to uterine vasodilatation.

Animals↗

Effects of hyperthermia on uterine blood flow and shunting through uterine arteriovenous anastomoses in the late-pregnant ewe.

The effect of maternal hyperthermia on uterine blood flow (UBF) through the two main uterine arteries and on the proportion of UBF shunted through uterine arteriovenous anastomoses (AVAs) was investigated. Eight late-pregnant ewes were exposed to normothermic (22-23 degrees C) or hyperthermic (approximately 39 degrees C) ambient conditions for 8 h. UBF was measured in the left and right uterine arteries using flow probes and microspheres were injected into the uterine artery before, during and after the experimental period. The distribution of microspheres between the uterus and lungs was determined to calculate changes in capillary and AVA blood flows. Hyperthermia produced a significant (P<0.05) increase in maternal core temperature (+1.5 degrees C), increase in maternal blood pH (+0.21; P<0.05) and decrease in maternal pCO2 (-16.2 mmHg; P<0.05). Blood flow to the uterine horn ipsilateral to the corpus luteum (CL) remained unchanged during hyperthermia, whereas total UBF and blood flow to the contralateral uterine horn were significantly decreased (P<0.05), by 23.1% and 20.8%, respectively, of pre-heat control values. The proportion of UBF shunted through uterine AVAs during hyperthermia was not significantly different from values observed in normothermic ewes (21.9 +/- 0.7%). Mild to moderate hyperthermia in late-pregnant sheep induces respiratory alkalosis and decreases total blood flow to the uterus, brought about by a decrease in blood flow to the uterine horn contralateral, but not ipsilateral to the CL. Heat treatment does not alter the proportion of UBF traversing uterine AVAs.

Animals↗

Effects of progesterone on expression of messenger RNA encoding oxytocin-neurophysin, oxytocin receptor and prostaglandin G/H synthase-1 and -2 during the early oestrous cycle in the ovine corpus luteum.

This study was conducted to determine whether early progesterone treatment plays a role in the regulation of messenger RNA (mRNA) expression for oxytocin-neurophysin, oxytocin receptor, prostaglandin G/H synthase (PGHS)-1 and PGHS-2 in the ovine corpus luteum. The expression of ovarian oxytocin, oxytocin receptor, PGHS-1 and PGHS-2 mRNA was investigated in control, progesterone- or RU486-treated ewes. Fifteen ewes were randomly assigned to three groups to receive intramuscular injections of progesterone (12.5 mg; n = 5), RU486, (2.5 mg kg(-1) bodyweight; n = 4) or corn oil (1 mL; n = 6) twice daily from Day 1 to Day 3 post oestrus. On the morning of Day 4 post oestrus, the corpora lutea were collected and analysed for oxytocin-neurophysin mRNA by Northern blot using a labelled cDNA probe, and for the expressions of the oxytocin receptor, PGHS-1 and PGHS-2 mRNA using the reverse transcription polymerase chain reaction. Administration of progesterone or suppression of progesterone activity with RU486 did not affect expression of oxytocin-neurophysin mRNA (P>0.05). Pretreatment of the ewes with progesterone resulted in the enhancement of luteal oxytocin receptor mRNA expression and suppression of PGHS-1 and PGHS-2 mRNA (P<0.001). These results indicate that early progesterone treatment does not control the expression of oxytocin-neurophysin mRNA in the ovine ovary but may be involved in the regulation of ovarian oxytocin receptor and PGHS expression. It is proposed, on the basis of these results, that progesterone may play a role in premature corpus luteum regression through an intra-ovarian mechanism involving the induction of ovarian oxytocin receptor mRNA expression.

Animals↗

Effect of labor induction on the expression of oxytocin receptor, cytochrome P450 aromatase, and estradiol receptor in the reproductive tract of the late-pregnant ewe.

UNLABELLED: In this study, we investigated the timing of changes in aromatase, estradiol receptor, and oxytocin receptor expression in ovine uterine and placental tissues before parturition. Labor was induced by betamethasone injection into the fetus on Days 130-132 of pregnancy. Tissue samples were collected at injection and then every 14 h until labor (56 h) from four ewes at each time point. Samples were analyzed for aromatase, estradiol receptor, and oxytocin receptor expression by in situ hybridization; for oxytocin binding to its receptor using a specific antagonist; and for estradiol receptor quantitation by immunocytochemistry. Aromatase mRNA expression increased by 14 h postinjection (p < 0.02) in the fetal villi and remained high until labor. Expression of estradiol and oxytocin receptor mRNAs was unchanged in myometrium but increased in the endometrial luminal epithelium by 28 h (p < 0.05) and remained high until labor. Estradiol receptor protein concentration increased modestly at labor while oxytocin receptor binding in the luminal epithelium changed in parallel to the mRNA concentration. IN CONCLUSION: 1) induction of aromatase may facilitate the expression of endometrial estradiol and oxytocin receptors in the placentome, 2) changes in endometrial rather than myometrial oxytocin receptor may be important in inducing parturition, and 3) the transcription of estradiol receptor and oxytocin receptor in the uterine epithelium are positively correlated during parturition.

Animals↗

Uterine milk protein, a novel activin-binding protein, is present in ovine allantoic fluid.

Activins are pluripotent growth factors that have recently been shown to be present in placental and fetal membrane preparations. Our previous studies have identified and purified activin A from ovine amniotic and allantoic fluids. In this study, ligand blots of side fractions from the isolation of activin A from allantoic fluid suggested the presence of activin-binding proteins other than follistatin. Further purification of one of these fractions involved two sequential reverse phase HPLC steps and a Superose 12HR fractionation. SDS-PAGE revealed a single protein band of 55 kDa, which was identified by NH2-terminal sequencing as ovine uterine milk protein (UTMP), a member of the serine protease inhibitor (serpin) superfamily of proteins. Further binding studies, using ligand blot techniques and Superose 12HR fractionation in the presence of [125I]activin, demonstrated UTMP to be an activin-binding protein with a lower affinity for activin than that of follistatin. A study of the specific binding behavior of UTMP to activin, using surface plasmon resonance, revealed an apparent equilibrium dissociation constant (Kd) of 49 +/- 25 nM, compared with the follistatin-activin Kd of 379 +/- 51 pM. Similar to another activin-binding protein, alpha2-macroglobulin, UTMP was unable to neutralize the bioactivity of activin in a bioassay based on the capacity of activin to inhibit the proliferation of an MPC-11 plasmacytoma cell line. The high concentrations of this protein in uterine fluid during pregnancy and its ability to bind activin suggest that UTMP may act as a low affinity, high capacity binding protein to sequester activin in the local uterine environment.

Activins↗

Oestrogenic effects of ICI 182,780, a putative anti-oestrogen, on the secretion of oxytocin and prostaglandin F2 alpha during oestrous cycle in the intact ewe.

The effect of ICI 182,780, oestrogen antagonist, on the concentration of oxytocin and uterine PGF2 alpha was investigated in intact Border Leicester Merino cross ewes during the late oestrous cycle. Twelve cyclic ewes (n = 6 per group) were randomly assigned to receive, at 6 h intervals, intra-muscular injection of either peanut oil or ICI 182,780 (1.5 mg kg-1 day-1) in oil for 2 days, starting at 1900 h on day 13 until 1300 h on day 15 post-oestrus. Hourly blood samples were collected via a jugular catheter from 0800 h on day 14 for 37 h and then daily over days 16, 17 and 18 post-oestrus. Peripheral plasma concentrations of oxytocin, the metabolite of prostaglandin F2 alpha, 15-keto-13,14-dihydro-prostaglandin F2 alpha, (PGFM) and progesterone were measured by radioimmunoassay. All ewes treated with ICI 182,780 exhibited functional luteal regression as indicated by a marked reduction in plasma progesterone concentrations to less than 1000 pg/ml over the period of 18-36 h during sampling period on days 14 and 15 of the oestrous cycle. In five of six vehicle-treated ewes, progesterone concentrations declined between day 16 and day 18 post-oestrus. In the remaining control ewe, progesterone concentrations reach less than 1000 pg/ml within 36 h of the commencement of the sampling period. During the frequent sampling period, the number of oxytocin pulses in the ICI 182,780 treated ewes was significantly higher compared to control ewes (2.7 +/- 0.3 vs. 0.8 +/- 0.3). The mean amplitude of oxytocin pulses observed was also greater (70.4 +/- 19.5 pg/ml) in ewes treated with ICI 182,780, but was not significantly different from the control ewes (33.5 +/- 12.9 pg/ml). Oxytocin pulses may however have occurred following the initial two ICI 182,780 injections but before commencing blood sampling. The oxytocin pulses were detected at a mean of 3.2 +/- 0.2 h following each injection with ICI 182,780 during blood sampling. In the ICI 182,780-treated ewes, the pulsatile pattern of plasma PGFM in jugular blood samples over the 37 h sampling period on days 14 and 15 post-oestrus had a higher amplitude (512.9 +/- 158.9 vs 121.7 +/- 78.7 pg/ml) and pulse area (618.1 +/- 183.3 vs 151.5 +/- 102.9 (ph/ml)tau) compared to the vehicle-treated ewes (P < 0.05) respectively.. The average number of PGFM pulses observed per ewe was 3.0 +/- 0.7 in the ICI 182,780-treated group and was significantly (P < 0.02) higher than the number of pulses (0.5 +/- 0.3) observed in ewes treated with vehicle alone. The PGFM pulses were detected at 4.2 +/- 0.6 h following each injection with ICI 182,780 during blood sampling. The percentage of PGFM pulses that occurred coincidently with significant elevation of oxytocin concentrations was 44.4% in ICI 182,780-treated compared to 66.6% in control ewes. We conclude that administration of oestrogen antagonist ICI 182,780 accelerated development of the luteolytic mechanism by enhancing pulsatile secretion of oxytocin and PGFM which suggests that ICI 182,780 acts as an agonist for oxytocin and prostaglandin f2 alpha release in intact ewes when administered at 1.5 mg/kg/day over day 13 to 15 post-oestrus.

Animals↗

Ovine allantoic fluid contains high concentrations of activin A: partial dissociation of immunoactivity and bioactivity.

In a preliminary study, allantoic fluid collected from pregnant sheep across gestational ages of 20-124 days contained significantly higher levels of activin bioactivity (189 +/- 74 ng/ml, mean +/- SE) than did amniotic fluid (3.2 +/- 0.6 ng/ml). Using a combination of chromatography steps, we isolated from 5 L of allantoic fluid approximately 612 microg of immunoactive activin, which eluted over 10 fractions from a C8 reversed-phase column. When these fractions were assayed in a rat pituitary cell culture bioassay, in a specific RIA, and in an activin A two-site ELISA, the RIA activity was skewed to the less hydrophobic side of the activin profile, while the bioactivity was skewed to the more hydrophobic forms. The activity measured in the two-site ELISA more closely matched the mass of activin as determined by laser densitometry. Amino-terminal sequencing of fractions containing either peak immunoactivity or bioactivity showed each to be identical to activin A. This was confirmed by internal sequences from a fraction that eluted in the area of overlapping immunoactivity and bioactivity. A peptide containing at least 18 amino acids at its amino terminus, which were identical to the conserved region of the acute-phase protein serum amyloid A, was identified in the most immunoactive activin fractions.

Activins↗

Physiological evidence for arteriovenous anastomoses in the uterine circulation of late-pregnant ewes.

1. The objective of the present study was to determine whether arteriovenous anastomoses (AVA) are present in the uterine circulation of conscious, late-pregnant ewes. 2. Twenty late-pregnant ewes were assigned to two groups. In group 1, 15 microm coloured microspheres were injected into the uterine artery of the pregnant horn and the relative proportion of microspheres trapped in the uterus and lungs was determined. The percentage shunting of blood measured by this method was 17+/-3%, representing a blood flow of 164+/-39 mL/min (n = 12). Any contribution of ovarian, cervical, rectal and other vascular beds was specifically excluded in this group. 3. In group 2, total uterine capillary flow was measured using the reference blood flow method, by injecting 15 microm microspheres into the heart. Calibrated flow probes, placed on both main uterine arteries, concurrently measured total uterine blood flow. Total blood flow to the uterus (flow probe) was significantly greater (t = 3.415; P = 0.027) than uterine capillary flow (microspheres), indicating AVA shunting in the uterine circulation. Mean total blood flow to the uterus was 1749+/-160 mL/min, of which an average 25+/-5% (n = 5 sheep) was shunted. 4. The percentage AVA shunting for groups 1 and 2 was not significantly different (t = 1.219; P = 0.24) and, when combined, the mean percentage of uterine blood flow passing through AVA in the late-pregnant sheep was determined to be 19+/-3%. 5. The present study shows that AVA are present and patent in the uterine circulation of late-pregnant ewes and that they account for the shunting of approximately 20% of the uterine blood flow into the maternal venous circulation.

Animals↗

Stimulation of ovarian oxytocin secretion and uterine prostaglandin release by exogenous progesterone early in the cycle of the ovarian auto-transplanted ewe.

The present study was undertaken to determine whether the administration of progesterone, early in the oestrous cycle, had an influence on ovarian oxytocin secretion and on peripheral concentrations of the prostaglandin F2 alpha metabolite 13,14-dihydro-15-keto PGF2 alpha (PGFM) in the ovarian auto-transplanted ewe. Twelve ewes with ovarian auto-transplants (n = 6 per group) were randomly assigned to receive an i.m. injection of progesterone (12.5 mg) or vehicle, twice a day, on days 1, 2 and 3 of the oestrous cycle. Beginning on day 7, blood samples were collected at intervals of 1 h from the ovarian and contralateral jugular veins for up to 70 h. Ovarian oxytocin secretion rate and jugular concentrations of PGFM and progesterone were determined by radioimmunoassay. The number of ewes that showed pulses of both ovarian oxytocin and PGFM was significantly (P < 0.05) greater in progesterone-treated ewes than in control ewes. In progesterone-treated ewes, the average number of ovarian oxytocin pulses per ewe was 9.66 +/- 5.5 (mean +/- SD) and the interval between pulses was 7.18 +/- 5.8 h. The mean amplitude and amount of oxytocin released, as calculated by the area under the curve of ovarian oxytocin pulses, were 6.27 +/- 1.98 ng min-1 and (10.05 +/- 8.91 ng min-1)tau, respectively (where tau is the number of hours between the last time point before and the first time point after a significant increase in hormone concentration was detected by the Pulsar program). The mean amplitude and area under the curve of PGFM pulses were 317.22 +/- 5.65 pg ml-1 and (383.36 +/- 1.77 pg ml-1)tau, respectively. The average number of pulses of plasma PGFM observed per ewe was 5.8 +/- 1.9 and interpulse interval for plasma PGFM pulses was 10.32 +/- 8.7 h between day 7 and day 9 after oestrus. These data indicate that administration of progesterone during the first 3 days of the oestrous cycle results in the premature release of ovarian oxytocin and uterine prostaglandin F2 alpha.

Animals↗

Changes in uterine endometrial phospholipids and fatty acids throughout the oestrous cycle and early pregnancy in the ewe.

This study examined changes in ovine endometrial phospholipids and fatty acid concentrations associated with luteolysis and the establishment of pregnancy in the ewe on days 3, 12 and 15, respectively. Results from this study indicate that endometrial lipids increased as the oestrous cycle progressed from days 3 to 12 and 15, whereas during early pregnancy, endometrial lipids decreased on day 15 of pregnancy when compared to days 3 and 12 of pregnancy. Phosphatidylcholine followed a similar pattern to that of total lipids, with an increase in phosphatidylcholine concentrations as the oestrous cycle progressed. During the early stages of pregnancy, phosphatidylcholine increased from day 3 to day 12, but then returned to previous levels by day 15 of pregnancy. Phosphatidylethanolamine increased late in the oestrous cycle, on day 15 as compared to days 3 and 12. This increase did not occur during early pregnancy, with phosphatidylethanolamine concentrations being constant from day 3 to day 15 of pregnancy. Both phosphatidylinositol and phosphatidylserine followed a similar pattern to phosphatidylethanolamine during the oestrous cycle and remained constant during early pregnancy. The fatty acid content of the major phospholipids involved in prostaglandin synthesis were examined over the range of fatty acids from C14:0 to C24:1omega9. Although changes in arachidonic acid were observed, there were no clear indications that these changes were directly related to the changes in PGF2alpha synthesis.

Animals↗

Effect of oestradiol on ovarian oxytocin secretion rate and luteolysis in the ewe after ovarian auto-transplantation.

The release of ovarian oxytocin and uterine prostaglandin (PG)F2alpha in response to an oestradiol stimulus was investigated. On Day 15 post-oestrus, ten ewes with ovarian auto-transplants (n=5 per group) received an intra-muscular injection of either oestradiol benzoate (50 microg) or vehicle. Blood samples were collected from the ovarian and jugular veins at 30 and 0 min before, and at 15-min intervals up to 540 min after, injection. The secretion rate of ovarian progesterone remained elevated in four of five treated ewes and in all control ewes, indicating the presence of a functional corpus luteum. Peripheral oestradiol concentrations were significantly (P < 0.001) higher in treated than in control ewes. The number of ewes that released pulses of ovarian oxytocin > or =240 min following oestradiol benzoate injection was significantly (P < 0 05) greater than that in control ewes. Mean amplitude and area under both ovarian-vein oxytocin and jugular-vein 15 keto-13,14 dihydro prostaglandin F2alpha (PGFM) pulses were significantly increased in the treated ewes. These findings demonstrate that the administration of exogenous oestrogen provides a positive stimulus for the release of ovarian oxytocin and uterine PGF2alpha in the ovarian auto-transplanted ewe.

Animals↗

Source of inhibin in ovine fetal plasma and amniotic fluid during late gestation: half-life of fetal inhibin.

Immunoactive inhibin (ir-inhibin) concentrations were determined in chronically catheterized sheep between 120 and 145 days gestation. Maternal plasma ir-inhibin concentrations remained basal (0.19 +/- 0.05 ng/ml) throughout the period of study. Immunoactive inhibin concentrations in male and female fetal plasma were elevated above those observed in maternal plasma, with the concentrations in plasma of male fetuses (7.38 +/- 0.04 ng/ml) being significantly greater (p < 0.001) than those in female fetuses (1.07 +/- 0.14 ng/ml). The concentrations of ir-inhibin in amniotic fluid of ewes bearing male fetuses (10.93 +/- 1.55 ng/ml) were significantly greater than in ewes bearing female fetuses (2.81 +/- 0.32 ng/ml; p < 0.05) but not significantly different from the concentrations in male fetal plasma. Immunoactive inhibin concentrations decreased following surgery in gonadectomized fetuses, to 3.25 +/- 0.99 ng/ml within 6 h, and remained at a mean value of 0.75 +/- 0.38 ng/ml from 24 h after gonadectomy. The half-life of circulating inhibin in fetal plasma, estimated from the decay curve during the first 6 h after surgery, was 3.94 +/- 0.88 h. There was a significant (p < 0.05) decrease in the concentration of ir-inhibin in amniotic fluid after gonadectomy; however, this decrease occurred gradually over 7 days, and ir-inhibin concentrations did not fall to those concentrations observed in fetal circulation at any time after gonadectomy. It is concluded that the major source of circulating ir-inhibin in male fetal plasma, but not in amniotic fluid, is the gonads.

Amniotic Fluid↗

Oxytocin receptor development in ovine uterus and cervix throughout pregnancy and at parturition as determined by in situ hybridization analysis.

The development of uterine oxytocin receptors is an important regulatory step in the initiation of labour. Paracrine production of oxytocin by uterine and placental tissues may also be involved in some species. Placentome, intercotyledonary endometrium, myometrium and fetal membranes were collected from 3-5 ewes each, at regular intervals throughout pregnancy and from eight ewes during labour. Localization of mRNA encoding oxytocin and its receptor was by in situ hybridization; oxytocin peptide concentrations were measured by radioimmunoassay and oxytocin receptor concentrations were measured by autoradiography and radioreceptor assay. In the intercotyledonary endometrium, mRNA encoding the oxytocin receptor was located in the luminal epithelium only. Both the epithelial and myometrial receptors were detected at low concentrations from the fourth week of gestation onwards, with a major increase associated with the onset of labour. In the placentomes, oxytocin receptors were localized to a stromal capsule surrounding the placental villi. Expression in this region was maximal in mid-gestation, declining in the second half of pregnancy and remaining low during labour. Cervical oxytocin receptors were detected at low concentrations in the epithelium and the muscular/connective tissue layers from day 22 of pregnancy onwards. There was no evidence for the local uterine production of oxytocin in the ewe; mRNA encoding oxytocin was undetectable and oxytocin concentrations were always < 23 pg g-1 wet mass of tissue. These results suggest that regulation of the timing of oxytocin receptor development varies between the different tissue types, despite a similar steroidal background. The receptors in the luminal epithelium are probably associated with the ability of exogenous oxytocin to induce the release of PGF2 alpha throughout most of pregnancy. The increase in receptors in both the intercotyledonary endometrium and myometrium at term suggest an involvement in labour, whereas their role in caruncular stroma in mid-pregnancy is unknown.

Analysis of Variance↗

Transplantation of cryopreserved fetal ovarian tissue to adult recipients in mice.

Sixteen-day-old fetal mouse ovaries were slowly frozen in 1.5 mol dimethylsulfoxide ml-1 and subjected to one of two thawing procedures--fast thaw or slow thaw. Fresh and frozen-thawed fetal ovaries were transplanted orthotopically (to the bursal cavity) to either bilaterally or unilaterally ovariectomized adult female recipients. Fresh fetal ovaries were also transplanted heterotopically (under the kidney capsule) to intact, bilaterally or unilaterally ovariectomized adult females. Transplantation of fetal ovaries to bilaterally ovariectomized adult recipients resulted in restoration of cyclic activity within 20.5 +/- 4.7 (mean +/- SEM) days or 23.4 +/- 0.8 days in orthotopic and heterotopic groups, respectively. Developing follicles and corpora lutea were observed within 4 weeks after transplantation of fetal ovaries to heterotopic sites and within 6 weeks after transplantation to orthotopic sites. After orthotopic transplantation, 33% of the recipients became pregnant. Orthotopic or heterotopic transplantation to intact of unilaterally ovariectomized recipients resulted in quiescence of the fetal ovary. After cryopreservation, transplantation of fetal ovaries to bilaterally ovariectomized recipients resulted in restoration of cyclic activity within 19.3 +/- 2.1 days and 23.4 +/- 5.1 days after transplantation in slow thaw and fast thaw groups, respectively. Fertility was restored to 86% of fast thawed and 25% of slow thawed fetal ovary transplants to bilaterally ovariectomized adult recipients. No ovarian tissue was observed on the side of the fetal graft in unilaterally ovariectomized recipients that received frozen-thawed fetal ovaries. These results demonstrate that cryopreserved fetal ovarian tissue can be transplanted to adult recipients with subsequent restoration of fertility and that this process is dependent on the absence of the ovaries of the recipients.

Animals↗

Implication of inhibin and related proteins in fetal development.

Initial studies on inhibin, activin and follistatin focussed on their role as regulators of adult gonadal function via feedback regulation of anterior pituitary hormones and via intragonadal control of steroid hormones. The discovery of isoforms of follistatin which are either secreted or retained on the cell surface and which bind activin and, to a lesser extent, inhibin adds a further dimension to the regulation of these peptides. More recently, the cloning of inhibin and activin, and the observation of their close homology to the transforming growth factor-beta family of peptides, has led to an interest in their possible role as growth and differentiation factors. Activin, inhibin and follistatin are expressed in embryonic and fetal tissues, as well as in the placenta. However, although activin is a potent regulator of growth and differentiation in a number of cell types, their role in embryonic and fetal development has yet to be established. High concentrations of inhibin have been observed in the fetal gonads, particularly the testes, and in the fetal adrenals of a number of species and a sex difference in fetal plasma concentrations has also been observed. Although the stimulus for high concentrations of inhibin in the fetus is not know, they are associated with decreased testicular testosterone and a decrease in the concentration of circulating follicle-stimulating hormone (FSH); this suggests that, as in the adult, inhibin may be involved in the regulation of fetal testicular androgen and pituitary FSH secretion during late gestation. The recent reports of elevated concentrations of inhibin and, particularly, activin in amniotic fluid during late gestation and its ability to stimulate the production of prostaglandin E2 by fetal membranes provides yet another potential role for this hormone in the regulation of events leading to parturition.

Activins↗

Oxytocin-induced prostaglandin F2 alpha release and endometrial oxytocin receptor concentrations throughout pregnancy in ewes.

Endometrial oxytocin receptor concentrations and oxytocin-induced plasma concentrations of 13,14,dihydro-15-keto prostaglandin F2 alpha were investigated on days 14 and 17 of the oestrous cycle and on days 14, 17, 25, 65, 85 and 145 of gestation in ewes. Total 13,14,dihydro-15-keto prostaglandin F2 alpha release in response to a bolus injection of oxytocin was significantly (P < 0.05) higher at luteolysis (day 17 of the oestrous cycle) than at any other stage of the oestrous cycle or in early gestation. On days 65, 85 and 145 of gestation, total prostaglandin release was significantly (P < 0.05) increased compared with earlier in gestation. Maximum concentrations of 13,14,dihydro-15-keto prostaglandin F2 alpha in response to oxytocin followed a similar pattern. Oxytocin receptor concentrations reflected total oxytocin-induced 13,14,dihydro-15-keto prostaglandin F2 alpha release, with increased oxytocin receptor concentrations occurring on day 17 of the oestrous cycle, compared with those observed on day 14 of the oestrous cycle and on days 14, 17 and 25 of gestation. By day 65 of gestation, oxytocin receptor concentrations were again increased. However, on days 85 and 145 of gestation, oxytocin receptor concentrations had decreased to concentrations similar to those observed in early gestation. These results indicate that oxytocin-induced 13,14,dihydro-15-keto prostaglandin F2 alpha release during early gestation is minimal despite the presence of endometrial oxytocin receptors. In mid-gestation, oxytocin-stimulated 13,14,dihydro-15-keto prostaglandin F2 alpha release is increased with a concomitant increase in uterine oxytocin receptor concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗