Plasma prostaglandin F2 alpha in the male Triturus carnifex (Laur.) during the reproductive annual cycle and effects of exogenous prostaglandin on sex hormones

Plasma patterns of prostaglandin F2 alpha (PGF2 alpha) and sex hormones (progesterone, androgens and 17 beta-estradiol) have been studied in the male crested newt, Triturus carnifex (Laur.), during the sexual cycle. The effects of exogenous PGF2 alpha on sex steroids have also been observed. In addition, effects of one week's captivity are reported. The patterns of plasma sex hormones, during the annual cycle, are consistent with the results previously reported for the same newt species. PGF2 alpha plasma level peaks in April, is low in summer, and progressively increases during autumn to peak again in December. The April PGF2 alpha peak coincides with a plasma estradiol increase and with an androgens drop. In April-collected newts, moreover, PGF2 alpha treatment induces a significant estradiol increase. These findings lead us to suppose that at the end of the breeding season (April) a PGF2 alpha-dependent estradiol synthesis occurs which could be implied in reproductive period termination. In several vertebrates, including some amphibian species, in fact, chronic administration of estradiol results in a strong inhibition of testicular endocrine tissue activity. The putative role of PGF2 alpha-dependent estradiol production in the gonadal regulation in amphibia living in temperate zones is discussed. The autumn PGF2 alpha increase has been tentatively related to the recovery gonadal processes and secondary sexual character development.     

Plasma prostaglandin F2 alpha and reproduction in the female Triturus carnifex (Laur.).

Plasma patterns of prostaglandin F2 alpha (PGF2 alpha) and sex hormones (progesterone, androgens and 17 beta-estradiol) have been studied in the female crested newt, Triturus carnifex (Laur.), during the annual sexual cycle. The effects of exogenous PGF2 alpha on sex hormones were determined. In addition, the effects of one week's captivity on plasma PGF2 alpha and sex hormones were reported. PGF2 alpha plasma level peaked in April, was low in summer, and progressively increased during the autumn to peak again in December. The April PGF2 alpha coincided with a 17 beta-estradiol rise, and with a progesterone drop. The autumn PGF2 alpha increase was coupled to a 17 beta-estradiol rise, and therefore it has been tentatively related to ovary and oviduct development. In newts collected in April, moreover, a PGF2 alpha-dependent 17 beta-estradiol synthesis could occur, since PGF2 alpha injection induced a significant 17 beta-estradiol plasma increase. These findings led us to suppose that PGF2 alpha intervenes in spring breeding season termination through the induction of a 17 beta-estradiol synthesis as in other amphibian species. PGF2 alpha injection caused a progesterone decrease, probably by inducing corpora lutea lysis. The patterns of plasma sex hormones were consistent with the results reported for the same newt species.     

Oestradiol and prostaglandin F2α regulate sexual displays in females of a sex-role reversed fish

The mechanisms regulating sexual behaviours in female vertebrates are still poorly understood, mainly because in most species sexual displays in females are more subtle and less frequent than displays in males. In a sex-role reversed population of a teleost fish, the peacock blenny Salaria pavo, an external fertilizer, females are the courting sex and their sexual displays are conspicuous and unambiguous. We took advantage of this to investigate the role of ovarian-synthesized hormones in the induction of sexual displays in females. In particular, the effects of the sex steroids oestradiol (E2) and testosterone (T) and of the prostaglandin F2α (PGF2α) were tested. Females were ovariectomized and their sexual behaviour tested 7 days (sex steroids and PGF2α) and 14 days (sex steroids) after ovariectomy by presenting females to an established nesting male. Ovariectomy reduced the expression of sexual behaviours, although a significant proportion of females still courted the male 14 days after the ovary removal. Administration of PGF2α to ovariectomized females recovered the frequency of approaches to the male''s nest and of courtship displays towards the nesting male. However, E2 also had a positive effect on sexual behaviour, particularly on the frequency of approaches to the male''s nest. T administration failed to recover sexual behaviours in ovariectomized females. These results suggest that the increase in E2 levels postulated to occur during the breeding season facilitates female mate-searching and assessment behaviours, whereas PGF2α acts as a short-latency endogenous signal informing the brain that oocytes are mature and ready to be spawned. In the light of these results, the classical view for female fishes, that sex steroids maintain sexual behaviour in internal fertilizers and that prostaglandins activate spawning behaviours in external fertilizers, needs to be reviewed.     

A possible role of prostaglandin E2 in reproduction of the male water frog, Rana esculenta. In vivo and in vitro studies.

Plasma prostaglandin E2 (PGE2), prostaglandin F2 alpha (PGF2 alpha), androgens and estradiol-17 beta were measured in the male water frog, Rana esculenta, during the annual sexual cycle. In vivo experiments were carried out to study the effects of PGE2 and PGF2 alpha on plasma sex steroids during the following periods: prereproduction (April), reproduction (May), postreproduction (June) and recovery (October). In the same months, in vitro experiments were performed to evaluate the effects of these two prostaglandins (PGs) on testicular release of sex steroids. The PGE2 plasma levels peaked in April. PGE2 treatment in vivo increased androgens in April and October, while PGF2 alpha increased estradiol-17 beta in June and October. In in vitro experiments, PGE2 increased androgens in April, while PGF2 alpha increased estradiol-17 beta in October. These results suggest that PGE2 could induce the breeding activity, probably through androgens synthesis. PGF2 alpha could interrupt the breeding, through estradiol-17 beta secretion.     

Relationships among mammalian gonadotropin-releasing hormone, prostaglandins, and sex steroids in the brain of the crested newt, Triturus carnifex.

The present study was carried out to evaluate the in vitro brain release of prostaglandin F2 alpha (PGF2 alpha), prostaglandin E2 (PGE2), androgens, and 17 beta-estradiol in male and female crested newt, Triturus carnifex, during three different periods of the annual sexual cycle; in addition, the effects of mammalian gonadotropin-releasing hormone (mGnRH), PGF2 alpha, and PGE2 on prostaglandins and steroids release by the brain were evaluated during the same periods. In brain incubations of both sexes, PGF2 alpha and estradiol were higher during postreproduction, while PGE2 and androgens were higher during reproduction. In both sexes, mGnRH increased PGF2 alpha and estradiol during postreproduction, and PGE2 during reproduction; PGF2 alpha increased estradiol secretion during postreproduction. Only in the male, did both mGnRH and PGE2 increase androgens during reproduction. It could be suggested that in Triturus carnifex, the regulation of the reproductive activity in the central nervous system (CNS) depends on the relationships among mGnRH, prostaglandins and steroids. In particular, PGF2 alpha and PGE2 seem to play different roles in the CNS of the newt: PGF2 alpha is involved in the postreproductive processes, through estradiol secretion, while PGE2 in the reproductive ones (through androgens secretion?).     

Elevated testosterone levels during nonbreeding-season territoriality in a fall-breeding lizard,Sceloporus jarrovi

Summary In many vertebrates, seasonal activation of sexual and territorial behaviors coincides with seasonal gonadal activation and is caused by the increase in sex steroid hormones. Both male and femaleSceloporus jarrovi are territorial, but in this species territorial behavior is seasonally activated in late April, months before seasonal gonadal maturation, which occurs in August prior to the fall mating season. Measurements of seasonal changes in circulating levels of the sex steroid hormones testosterone, progesterone, and estradiol indicated that testosterone levels in both sexes are elevated when territorial behavior is expressed, even during the period of nonbreeding-season territoriality during the summer. This suggests that a nonbreeding season behavior is activated by a sex steroid hormone in this species.     

Sexual Fate Reprogramming in the Steroid-Induced Bi-Directional Sex Change in the Protogynous Orange-Spotted Grouper,Epinephelus coioides

Androgen administration has been widely used for masculinization in fish. The mechanism of the sex change in sexual fate regulation is not clear. Oral administration or pellet implantation was applied. We orally applied an aromatase inhibitor (AI, to decrease estrogen levels) and 17α-methyltestosterone (MT, to increase androgen levels) to induce masculinization to clarify the mechanism of the sex change in the protogynous orange-spotted grouper. After 3 mo of AI/MT administration, male characteristics were observed in the female-to-male sex change fish. These male characteristics included increased plasma 11-ketotestosterone (11-KT), decreased estradiol (E2) levels, increased male-related gene (dmrt1, sox9, and cyp11b2) expression, and decreased female-related gene (figla, foxl2, and cyp19a1a) expression. However, the reduced male characteristics and male-to-female sex change occurred after AI/MT-termination in the AI- and MT-induced maleness. Furthermore, the MT-induced oocyte-depleted follicle cells (from MT-implantation) had increased proliferating activity, and the sexual fate in a portion of female gonadal soma cells was altered to male function during the female-to-male sex change. In contrast, the gonadal soma cells were not proliferative during the early process of the male-to-female sex change. Additionally, the male gonadal soma cells did not alter to female function during the male-to-female sex change in the AI/MT-terminated fish. After MT termination in the male-to-female sex-changed fish, the differentiated male germ cells showed increased proliferating activities together with dormancy and did not show characteristics of both sexes in the early germ cells. In conclusion, these findings indicate for the first time in a single species that the mechanism involved in the replacement of soma cells is different between the female-to-male and male-to-female sex change processes in grouper. These results also demonstrate that sexual fate determination (secondary sex determination) is regulated by endogenous sex steroid levels.     

Luteolysis, estrus and ovulation, and blood prostaglandin F after intramuscular administration of 15, 30 or 60 mg prostaglandin F2α

During diestrus in three consecutive estrous cycles, each of six heifers was given (im) 30 mg, 15 mg (twice at 6-hr intervals) and 60 mg prostaglandin F_2α (PGF_2α) tham salt. Neither the decline in blood progesterone, the increase in blood estradiol, the duration or the peak of the LH surge, the interval to onset of estrus, nor the interval to ovulation was affected significantly by dose of PGF_2α. Thus, relative to that after 30 mg PGF_2α im, two injections of 15 mg at 6-hr intervals or 60 mg PGF_2α did not hasten luteolysis. Thirty mg was an ample im dose of PGF_2α to cause luteolysis. Regardless of im dose of PGF_2α, blood PGF peaked at about 6.0 ng/ml within 10 minutes and returned to basal values (<1.0 ng/ml) within 90 minutes. In another trial, after a single iv injection of 5 mg PGF_2α, blood PGF peaked (25 ng/ml) within 5 minutes and returned to basal values within 15 minutes. During a 30-minute infusion (0.5 mg/minute) of PGF_2α, blood PGF plateaued at 29.5 ng/ml with a metabolic clearance rate of 17.0 liters per minute.     

Relationships among mammalian gonadotropin-releasing hormone, prostaglandins, and sex steroids in the brain of the crested newt, Triturus carnifex

The present study was carried out to evaluate the in vitro brain release of prostaglandin F_2α (PGF_2α), prostaglandin E₂ (PGE₂), androgens, and 17β-estradiol in male and female crested newt, Triturus carnifex, during three different periods of the annual sexual cycle; in addition, the effects of mammalian gonadotropin-releasing hormone (mGnRH), PGF_2α, and PGE₂ on prostaglandins and steroids release by the brain were evaluated during the same periods. In brain incubations of both sexes, PGF_2α and estradiol were higher during postreproduction, while PGE₂ and androgens were higher during reproduction. In both sexes, mGnRH increased PGF_2α and estradiol during postreproduction, and PGE₂ during reproduction; PGF_2α increased estradiol secretion during postreproduction. Only in the male, did both mGnRH and PGE₂ increase androgens during reproduction. It could be suggested that in Triturus carnifex, the regulation of the reproductive activity in the central nervous system (CNS) depends on the relationships among mGnRH, prostaglandins and steroids. In particular, PGF_2α and PGE₂ seem to play different roles in the CNS of the newt: PGF_2α is involved in the postreproductive processes, through estradiol secretion, while PGE₂ in the reproductive ones (through androgens secretion?).     

Changes in hormonal profile, gonads and sperm quality of Argyrosomus regius (Pisces, Scianidae) during the first sexual differentiation and maturation

In the present study, sexual gonadal differentiation and first sexual maturation of Meagre (Argyrosomus regius) was studied, based upon the annual changes in gonadosomatic index (GSI), gonadal histology, and the plasma steroid hormones, testosterone (T), 11-ketotestosterone (11-KT), and estradiol (E2). In addition, spermatozoa characteristics were evaluated by measuring sperm motility and morphology. Results demonstrated that Meagre completes sex differentiation at 10 to 12 mo of age, and are group-synchronous spawners, which reach puberty at 2 (mean length 26.8 ± 0.7 cm, mean weight 920 ± 75 g; N = 10) and 3 (mean length 35.8 ± 0.8 cm, mean weight 1610 ± 89 g; N = 10) years of age for males and females, respectively. In males, during the sex differentiation period, T levels were significantly higher with respect to those of 11-KT; this suggests that T has a key role in the early phases of the sex differentiation. During the spawning season an increase in plasma concentrations of all hormones was observed with 11-KT levels being significantly higher that those of T. In females, during the sex differentiation period, there was an increase in E2 plasma levels, while during the first spawning season, a significant increase of T and E2 levels were measured. Regarding sperm characteristics, the measured curvilinear velocity (VCL) and straight-linear velocity (VSL), resulted in the same order of magnitude with respect to those measured in other marine fish, while the average path velocity (VAP) was similar to that measured in the European Eel. The head of Meagre spermatozoa presents as oval shaped with a surface area of approximately 3.66 μm² and a perimeter of approximately 6.65 μm. All these findings represent an important basis for further investigation on the reproductive biology of this specie and may assist the farmers to improve seed production in aquaculture.     

The effect of prostaglandin F2α on the activator calcium of the uterus

The mechanism through which PGF2_α exerts its oxytocic action was studied in 150 uterine strips, 48 excised from 25 days pregnant and 102 from post partum rabbits. PGF2_α delayed the loss of excitability upon exposure of the uterus to Ca-free Krebs Ringer Bicarbonate (KRB) solution and accelerated recovery when half (1.25 mM) of the normal CaCl₂ was replaced in the KRB. This effect of PGF2_α was more pronounced in the post partum than the pregnant uterus, which resisted Ca-deficiency by high affinity binding in its plasma membrane of the activator-Ca (A-Ca).The Ca-ionophore A23187 simulated the action of PGF2_α but only during stimulation with 12 V/5 cm and not with 60 V/5 cm. This finding suggests that while the effect of PGF2_α is limited to a control of the movement of the extracellular and membrane-bound Ca, A23187 affects the distribution of Ca liberated by the strong (60 V/5 cm) electric field from internal stores of the myometrial cells. In the presence of Ruthenium-red (a Ca-influx inhibitor) and only 1.25 mM CaCl₂, PGF2_α restored excitability slowly, indicating that PGF2_α is an oxytocic agent because it promotes Ca-influx. However, knowing that Ca-efflux is in part dependent upon Ca-influx the most informative present finding was the observation that PGF2_α did not promote ⁴⁵Ca-efflux when ⁴⁰Ca-influx was inhibited by Verapamil. This demonstration provided more direct evidence that PGF2_α promotes the influx of the A-Ca and thus explained the mechanism of action of this key regulator at the molecular level.     

Prostaglandin F in the peripheral plasma of the rhesus monkey in normal pregnancy and after the administration of dexamethasone and PGF2α

The concentration of prostaglandin F (PGF) has been measured in the peripheral plasma of normal rhesus monkeys ( ) during the final third of gestation, and in monkeys treated with dexamethasone or PGF₂α after day 145 of pregnancy. Daily administration of PGF₂α (10–15 mg/day im) reliably induced abortion within 3–6 days. However, dexamethasone (8 mg/day im from day 145) had no effect on the length of gestation.The concentration of PGF in the femoral venous plasma of untreated or dexamethasone-treated monkeys was highly variable, both in serial samples taken from the same animal and in samples taken from different animals at the same time of gestation. There was no indication of an effect of dexamethasone treatment on the plasma PGF levels, nor did the concentration of PGF increase during late pregnancy before spontaneous parturition. These results show that the myometrium of the pregnant rhesus monkey is highly sensitive to exogenous PGF₂α during late gestation. However, a significant increase in the peripheral plasma concentration of PGF prior to the onset of labor was not observed.     

Secretion rate of prostaglandin F during induced labor in goats

Relationships between plasma flow and plasma concentrations of prostaglandin F were examined in the utero-ovarian veins of three pregnant goats. Plasma flow, measured by veno-arterial dilution of para-Aminohippurate in two goats, was unchanged or increased slightly when PGF concentrations were elevated by short-term infusions of PGF_2α into a uterine vein. Utero-ovarian plasma flow was measured during labor in two goats. Flow doubled during advanced labor and then decreased sharply to very low rates during the terminal expulsive phase of stage II labor.A total of 8.3 and 9.5 mg PGF was released into the utero-ovarian vein of two goats during the last 6 hours before fetal delivery and maximal release rates of approximately 100 ug. min⁻¹ were obtained some 5–10 minutes before delivery was completed. The highest plasma concentrations of PGF were detected immediately after completion of fetal delivery when utero-ovarian plasma flows were lowest.     

Stimulation by prostaglandin F2α of acidic glycosaminoglycan production in cultured fibroblasts

The effect of PGF2α on the synthesis of hexosamine-containing substances (acidic glycosaminoglycans and glycoproteins) was studied in cultured fibroblasts derived from a rat carrageenin granuloma. Treatment with PGF2α ranging from 0.01 μg/ml to 20 μg/ml resulted in a significant increase of the production of these macromolecules by the cells. The stimulatory effect was found significant even at the low concentration of 10 ng/ml, and could be seen as early as 3h after exposure to PGF2α. The hexosamine-containing substances increased by PGF2α revealed that 80% of the increase was due to acidic glycosaminoglycans and the rest was due to glycoproteins.     

Progesterone, 20α-dihydroprogesterone and PGF; Interrelated hormonal changes during pseudo-pregnancy in the rat

Ovarian and uterine tissue concentrations of progesterone, 20α-dihydroprogesterone (20_αOHP) and prostaglandin F (PGF) were measured during hormonally-induced pseudopregnancy, as were plasma levels of progesterone and 20αOHP, in hysterectomised and sham-operated rats. Elevated levels of PGF in uterine and ovarian tissues were coincident with declining concentrations of progesterone and increasing concentrations of 20αOHP in the sham-operated rats. Maximum PGF concentrations were apparent in uterine tissue 14 days after hCG injection, coincident with the plasma, ovarian and uterine nadir concentrations of progesterone. A small but statistically significant increase in ovarian PGF was apparent at this time in sham-operated rats. This elevation of ovarian PGF was abolished by hysterectomy.     

Effects of epinephrine and oxytocin on the release of prostaglandin F from the rat uterus in vitro

Isolated uteri from rats with regular 4-day cycles were incubated in Krebs-Ringer bicarbonate buffer and the release of PGF into the medium was measured by radio-immunoassay after extraction of the incubation medium with ethyl acetate at pH 3.0–3.5. PGF was produced from endogenous precursors and accumulated in equal amounts in the medium during two successive 60 min periods on each day of cycle, but the magnitude of the production varied significantly during the cycle, being greatest in estrus. Oxytocin in doses up to 500 mU/ml had no effect on PGF accumulation in the incubation period at any stage of the cycle, while epinephrine (10⁻³) greatly stimulated PGF release from the estrous uterus but had no effect on PGF release from the diestrous uterus. Phentolamine, an α-blocking agent, had no effect on the epinephrine-induced release of PGF, while propranolol, a β-blocking agent, not only prevented the increase in PGF production induced by epinephrine but also reduced the basal release of PGF by the estrous uterus. Since oxytocin contracts and epinephrine relaxes the nonpregnant rat uterus both in vivo and in vitro, it is unlikely that the effects of these two compounds on uterine contractility are mediated by the release of PGF_2α.     

Zonal heterogeneity of prostaglandin and thromboxane release in the dog kidney

The release of prostaglandin(PG) and thromboxane(TX) was examined in the six different areas of the normal dog kidney, i.e., renal arterial and venous strips(RA and RV), superficial and deep cortical slices (SC and DC) and outer and inner medullary slices(Om and IM). These tissues were incubated in Krebs-bicarbonate buffer(pH 7.4, 37°C), and the released PGE2, PGF2α, 6-keto-PGF1α and TXB2(as stable metabolites of PG12 and TXA2, respectively) were determined by radioimmunoassay. In RA, RV, SC and DC, 6-keto-PGF1α was predominant, however, there were no quantitative differences between RA and RV, or SC and DC. The release of 6-keto-PGF1α reached a maximum in IM, similar to findings on the release of PGE2 and PGF2α. The release of TXB was uniform in OM and IM. The amount of PGE2, PGF2α, 6-keto-PGF1α and TXB2 released from IM was 2800, 400, 60 and 50 times higher, respectively, than the extent of the release from the cortical slices.These results suggest that PG12 as well as PGE2 and PGF2α, may be involved in renal PG, and that TXA2 is biosynthesized in the normal dog kidney.     

Temporal response of uterine prostaglandins to estradiol treatment in the ovariectomized-prenant rat

Previous studies in our laboratory have shown that 24 hours of estradiol treatment significantly enhanced uterine prostaglandin (PG)F, PGE and thromboxane B₂ (TxB₂) leels but had no effect on 6-Keto-PGF_1α (6KF) concentrations in ovariectomized-pregnant rats. One explanatior for the lack of an augmentation in 6KF was a temporal differences in response (i.e. 6KF increased and decreased within the 24 hour period). To test this possibility rats were ovariectomized on day 19 of pregnancy and sacrificed 0, 4, 8, 12, 16, 20 and 24 hours after estradiol treatment. Uterine tissue and venous plasma were analyzed for PGs by radioimmunoassay. No significant (p > .05) alterations were detected for any of the uterine PGs at 0, 4, 8 and 12 hours. However, at 16 hours PGF, TxB₂ and PGE all showed significant (p > .05) increases (2.4, 3.4 and 2.1 fold, respectively) compared to 12 hours. In contrast, no significant augmentation in 6KF levels (p > .05, 1.3 fold) was detected at 16 compared to 12 hours although it was enhanced relative to 0 and 4 hours. In addition, PGF, TxB₂ and PGE, but not 6KF, showed further increases 24 hours after estradiol administration. No alterations were found (p > .05) for any of the PGs in uterine venous plasma at the time points studied. In summary, uterine PGF, PGE and TxB₂ net production appears to be more enhanced by estradiol treatment than 6KF at the time points studied. In addition, there is a slight, but significant, difference in the temporal response characteristics of 6KF compared to the other PGs. The data suggest that the dramatic increase in uterine PGF, PGE and TxB₂ levels at parturition in the rat are probably significantly related to enhanced levels of estradiol. However, the majority of the increase in uterine 6KF levels at labor is more likely caused by factors other than augmented plasma estradiol.     

Uterine activity and prostaglandin production following intraamniotic hyperosmolar urea

The relationship between endogenous prostaglandin (PG) production and uterine activity was studied in hyperosmolar urea induced abortion patients. Polygraphic recordings of intraamniotic pressure were obtained at periodic intervals following intraamniotic injection of 80 gm urea. At 0, 0.25, 1, 4 and 8 hours amniotic fluid and blood samples were obtained for PGE, PGF and 13,14-dihydro-15-keto-prostaglandin F_2α (PGFM) analysis by radioimmunoassay. Blood was also sampled at time of absorption. In eight patients studies, uterine tone was elevated by 0.25 hour although no rhythmic contractions were observed by 1 hour. At 4 hours, amniotic fluid PGF concentration increased significantly (P < .01) over the pre-injection value and continued to increase at 8 hours. Amniotic fluid PGE, PGFM and all plasma PG's showed no change during the 8 hour period following urea administration. At time of abortion the plasma PGFM concentration was significantly greater than at the time of injection (238 ± 54.4 vs. 86.7 ± 7.3 pg/ml). There was no significant differences between pre-injection and absorption plasma PGF or PGE concentrations. In the present study, there is no evidence that increased prostaglandin production precedes urea induced contractions. The possible role of PG's in uterine contractions is discussed.     

Production of prostaglandin Fα in ewes following luteal regression induced with a prostaglandin analogue, Estrumate (cloprostenol; I.C.I. 80996)

A single injection (100μg i.m.) of Estrumate (I.C.I. 80996) was used to induce luteal regression on day 8 of the estrous cycle in 3 sheep. Progesterone levels in the utero-ovarian vein and femoral artery had fallen within 6 h to <50% of the concentrations seen before injection of the analogue. Luteolysis was not associated with endogenous production of PGF. The concentration of PGF in the utero-ovarian vein began to increase 27–39 h after the administration of Estrumate, reaching a mean maximum concentration of 1455pg/ml 48 h after Estrumate. The mean concentration of PGF in the utero-ovarian vein between 36–69 h after Estrumate was significantly greater than during the 24 h before Estrumate (control period) or during the 0–30 h immediately after injection (both P < 0.001). The maximum secretion of estradiol and the pre-ovulatory LH peak occurred during the period of elevated PGF concentrations in the utero-ovarian veins. The possible importance of endogenous PGF production at this time is discussed.