Effects of a cholesterol esterase inhibitor and of prostaglandin F2α on testis cholesterol and on plasma testosterone in mice

Administration of Phenylmethylsulfonylfluoride, an inhibitor of cholesterol esterase, to male mice caused an increase in the concentration of esterified cholesterol in the testis, a decrease in the weight of seminal vesicles and a decrease in the concentration of testosterone in peripheral plasma. It is suggested that hydrolysis of cholesterol esters present in the testis is required for normal production of androgenic steroids.Administration of prostaglandin F_2α to male mice lowered plasma testosterone levels and raised the concentration of esterified cholesterol in the testes. Apparently testicular steroidogenesis was inhibited.     

Increase in progesterone and luteal blood flow without a luteolytic response after prostaglandin F2α treatment in early luteal-phase heifers

Acute changes in circulating progesterone concentration and luteal blood flow in heifers after a conventional dose of prostaglandin F(2α) (PGF; 25mg dinoprost, i.m.) were compared between the early luteal phase (Day 3) and midluteal phase (Day 10; Day 0=ovulation), using four groups (Day-3 control, Day-3 PGF, Day-10 control, and Day-10 PGF; n=6 heifers/group). Blood samples were collected at 0, 2, 5, 10, 15, 30, 60, and 120 min (0 min=treatment). Percentage of luteal area with color-Doppler blood-flow signals was estimated at 0, 10, and 30 min. In the Day-3 and Day-10 PGF groups, progesterone increased to a peak at 15 min. In the Day-3 PGF group, progesterone decreased to the pretreatment concentration by 60 min but did not decrease to below the pretreatment concentration during the 2-h experimental period. In the Day-10 PGF group, progesterone decreased to below pretreatment concentration by 30 min, indicating a luteolytic response. In the Day-3 and Day-10 PGF groups, luteal blood flow increased within 10 min and remained elevated until the last examination at 30 min. The absence of a decrease in progesterone to below pretreatment concentrations in the Day-3 PGF group indicated that luteolysis does not necessarily follow a transient increase in progesterone and a concomitant increase in luteal blood flow. The immediate transient increase in progesterone and an increase in luteal blood flow without a subsequent decrease in progesterone to below pretreatment concentrations after PGF treatment in early luteal-phase heifers are novel findings.     

Effects of indomethacin and prostaglandin F2α on ovulation and ovarian contractility in the rabbit

The present investigation was carried out to determine whether inhibition of ovulation in the rabbit by administration of indomethacin can be correlated with any change in ovarian contractility at ovulation time and can be reversed by administration of prostaglandins. Indomethacin was adminstered intra-muscularly using three different schedules in a dose of 5 mg/kg. A reduced number of ruptured follicles following HCG was noted in all groups treated with indomethacin. Infusion of PGF_2α into the aorta (1 μg/kg/min.) could reverse this effect. Less pronounced ovarian contractility was observed after indomethacin treatment, but infusion of PGF_2α immediately enhanced contractility in ovaries from indomethacin treated rabbits. The inhibition of ovulation in the rabbit associated with indomethacin adminstration may be related to suppression of ovarian contractions. These data also suggest that prostaglandins may play a significant role in the mechanism of ovulation through an influence on ovarian contractility.     

Enzymatic formation of prostaglandin F2α in human brain

Prostaglandin (PG)E₂ 9-ketoreductase, which catalyzes the conversion of PGE₂ to PGF₂, was purified from human brain to apparent homogeneity. The molecular weight, isoelectric point, optimum pH, Km value for PGE₂, and turnover number were 34,000, 8.2, 6.5–7.5, 1.0 mM, and 7.6 min^–1, respectively. Among PGs tested, the enzyme also catalyzed the reduction of other PGs such as PGA₂, PGE₁, and 13,14-dihydro-15-keto PGF₂, but not that of PGD₂, 11-PGE₂, PGH₂, PGJ₂, or ¹²-PGJ₂. The reaction product formed from PGE₂ was identified as PGF₂, by TLC combined with HPLC. This enzyme, as is the case for carbonyl reductase, was NADPH-dependent, preferred carbonyl compounds such as 9,10-phenanthrenequinone and menadione as substrates, and was sensitive to indomethacin, ethacrynic acid, and Cibacron blue 3G-A. The reduction of PGE₂ was competitively inhibited by 9,10-phenanthrenequinone, which is a good substrate of this enzyme, indicating that the enzyme catalyzed the reduction of both substrates at the same active site. These results suggest that PGE₂ 9-ketoreductase, which belongs to the family of carbonyl reductases, contributes to the enzymatic formation of PGF₂ in human brain.Special issue dedicated to Dr. Sidney Udenfriend.     

Colocalization of prostaglandin F2�� receptor FP and prostaglandin F synthase-I in the spinal cord

Prostaglandin F_2α is synthesized by prostaglandin F synthase, which exists in two types, prostaglandin F synthase I (PGFS I) and prostaglandin F synthase II (PGFS II). Prostaglandin F_2α binds to its specific receptor, FP. Our previous immunohistochemical study showed the distinct localization of prostaglandin F synthases in rat spinal cord. PGFS I exists in neuronal somata and dendrites in the gray substance, and PGFS II exists in ependymal cells and tanycytes surrounding the central canal. Both enzymes are also present in endothelial cells of blood vessels in the white and gray substances of the spinal cord. In this study, we found that FP localizes in neuronal somata and dendrites but not in ependymal cells, tanycytes, or endothelial cells. Immunohistochemical analysis of serial sections showed the colocalization of FP and PGFS I. FP immunoreactivity was intense in spinal laminae I and II of the dorsal horn, a connection site of pain transmission, and was similar to that of PGFS I in neuronal elements. These findings suggest that prostaglandin F_2α synthesized in the neuronal somata and dendrites exert an autocrine action there.—Suzuki-Yamamoto, T., K. Toida, Y. Sugimoto, and K. Ishimura. Colocalization of prostaglandin F_2α receptor FP and prostaglandin F synthase-I in the spinal cord.     

Effect of progesterone administration on the release of uterine prostaglandin F2α and ovarian oxytocin in the goat

The effects of intramuscular progesterone administration (20 mg·day⁻¹) on plasma concentrations of 13,14-dihydro-15-keto-prostaglandin F_2α (PGFM-pulmonary metabolite of prostaglandin F_2α) and oxytocin were examined in seventeen goats after either bilateral ovariectomy, hysterectomy or during days 12–16 of the estrous cycle. Daily mean values of PGFM in animals treated with progesterone after ovariectomy were significantly greater (P<0.001) than in their corresponding controls on the last two treatment days (10 and 11); concentrations of oxytocin, however, remained at or near the limits of assay sensitivity. In hysterectomized goats PGFM concentrations remained extremely low and oxytocin release appeared steady rather than pulsatile. In the intact animals, undergoing luteolysis, daily mean concentrations of both PGFM and oxytocin were significantly greater (P<0.01) in progesterone-treated goats than in their oil-treated controls; furthermore, in the progesterone-treated goats, increases in PGFM concentrations, observed after the peaks of progesterone, were either coincident with or prior to pulses of oxytocin. These results demonstrate that uterine PGF_2α stimulates the pulsatile release of oxytocin from the ovary during luteolysis in the goat.     

Changes in prostaglandin E2 and F2α during vitellogenesis in the florida crayfish Procambarus paeninsulanus

While the role of eicosanoids in reproduction in vertebrate species has been well established, the role of these fatty acid derivatives in invertebrate species has not been as well characterized. The purpose of this study was to investigate changes in prostaglandins E₂ and F₂ during vitellogenesis in the crayfish Procambarus paeninsulanus. In homogenates of crayfish ovaries taken at various stages of development, the rate of prostaglandin synthesis and the concentrations of prostaglandins E₂ and F₂ increased during the final stages of yolk production just prior to ovulation. A gradual increase in prostaglandin E₂ amounts was observed throughout the progression of vitellogenesis. The data suggests the possible involvement of prostaglandins in regulatory events associated with vitellogenesis and the induction of ovulation in Procambarus paeninsulanus.Abbreviations EIA enzyme immunoassay kit - GIH gonad inhibiting hormone - HPLC high-pressure liquid chromatography - PGE₂ prostaglandin E₂ - PGF₂ prostaglandin F₂ - RIA radioimmuno assay - SNK Student-Newman-Keuls multiple t-test - TLC thin-layer chromatography     

Effects of inhibition of prostaglandin F2α biosynthesis during preluteolysis and luteolysis in heifers

Flunixin meglumine (FM; 2.5 mg/kg) was given to heifers at three 8-h intervals, 16 d after ovulation (first treatment = Hour 0) to inhibit the synthesis of prostaglandin F_2α (PGF), based on plasma concentrations of a PGF metabolite (PGFM). Blood samples were collected at 8-h intervals from 15 to 18 d in a vehicle (control) and FM group (n = 16/group). Hourly samples were collected from Hours −2 to 28 in 10 heifers in each group. Heifers that were in preluteolysis or luteolysis at Hour 0 based on plasma progesterone (P4) concentrations at 8-h intervals were partitioned into subgroups. Concentration of PGFM was reduced (P < 0.05) by FM treatment in each subgroup. For the preluteolytic subgroup, the first decrease (P < 0.05) in P4 concentration after Hour 0 occurred at Hours 24 and 40 in the vehicle and FM groups, respectively. Plasma P4 concentrations 32 and 40 h after the beginning of luteolysis in the luteolytic subgroup were greater (P < 0.05) in the FM group. Concentration at the peak of a PGFM pulse in the FM group was greater (P < 0.05) in the luteolytic than in the preluteolytic subgroup. The peak of a PGFM pulse occurred more frequently (P < 0.001) at the same hour as the peak of an LH fluctuation than at the ending nadir of an LH fluctuation. In conclusion, a reduction in prominence of PGFM pulses during luteolysis delayed completion of luteolysis, and treatment with FM inhibited PGFM production more during preluteolysis than during luteolysis.     

Comparison of the pulmonary vascular response to prostaglandin A1, prostaglandin F2α and angiotensin II; Metabolism of PGA1 in lung

A rabbit lung preparation, perfused $\text{in vitro}$, was used to examine pulmonary metabolism of prostaglandin A₁ (PGA₁) and to compare the vasoconstrictor actions of PGA₁, prostaglandin F_2α (PGF_2α) and angiotensin II. PGF_2α caused significantly more, and angiotensin II significantly less, vasoconstriction than did an equimolar concentration of PGA₁. Of three likely PGA₁ metabolites only 15-keto-PGA₁ had any significant vasoconstrictor action. Furosemide and aminophylline (10^?3 M) reduced PGA₁, PGF_2α or angiotensin II-induced vasoconstruction. Diphloretin phosphate potentiated the vascular effect of angiotensin II. Furosemide (10^?3 M) and DPP (9.5 × 10^?6 M) significantly reduced pulmonary metabolism of PGA₁ while aminophylline (10^?3 M) had no effect on this process. Perfusion of the lungs with a hypoxic medium had no effect on PGA₁ metabolism.     

Luteal progesterone and prostaglandin F2α production invitro during fluprostenol-induced luteolysis in the mare

Prostaglandin F₂α (PGF₂α) release $\text{in}$$\text{vitro}$ by luteal tissue from mares was quantified to determine if exogenous prostaglandin analog increased endogenous luteal PGF₂α production during induced luteolysis. On day 8 after ovulation, luteal tissue was collected by flank laparotomy and endometrium was collected by uterine biopsy. Mares were assigned to one of four treatments: (1) no intramuscular injection at 0-hr (n = 5), (2) 250 μg Fluprostenol (ICI 81008 PGF₂α analog) at 4-hr (n = 4), (3) 250 μg Fluprostenol at 12-hr (n = 5), or (4) 250 μg Fluprostenol at 28-hr (n = 5) prior to tissue collection at laparotomy. Blood was collected from a jugular vein at laparotomy. Luteal and endometrial tissues (100-mg minces) were incubated in duplicate in 5 ml of Krebs-Ringer bicarbonate buffer (pH 7.4) in an ice bath in an air atmosphere or at 37°C in an atmosphere of 95% O₂:5% CO₂. The incubation treatments consisted of: no treatment, indomethacin 1.3 × 10^?4M, 1 μg/ml of arachidonic acid, 10 μg/ml of Fluprostenol, and 100 μM dbc-AMP (Fluprostenol was not added to endometrial tissue incubations). The injection of Fluprostenol induced luteolysis in these mares as indicated by decreased plasma progesterone and luteal tissue progesterone production (P<0.01). Luteal PGF₂α production was only detectable in tissue from mares that had been injected with Fluprostenol; production reached a maximum by 12 hr post-injection and had returned to pre-treatment levels by 28 hr (P<0.01). Endometrial tissue produced PGF₂α, but this activity was not significantly affected by injection of mares with Fluprostenol. Increased production of PGF₂α by luteal tissue of mares during PGF₂α analog induced luteolysis was similar to that observed in the pig and ewe.     

Bioactive eicosanoids: Role of prostaglandin F2α and F2-isoprostanes in inflammation and oxidative stress related pathology

Oxidative stress and inflammation are supposed to be the key players of several acute and chronic diseases, and also for progressive aging process. Eicosanoids, especially prostaglandin F_2α (PGF_2α) and F₂-isoprostanes are endogenous compounds that are involved both in physiology and the above mentioned pathologies. These compounds are biosynthesized mainly from esterified arachidonic acid through both enzymatic and non-enzymatic free radical-catalysed reactions in vivo, respectively. They have shown to possess potent biological activities in addition to their application as biomarkers of oxidative stress and inflammation. Recent advancement of methodologies has made it possible to quantify these compounds more reliably and apply them in various in vivo studies successfully. Today, experimental and clinical studies have revealed that both PGF_2α and F₂-isoprostanes are involved in severe acute or chronic inflammatory conditions such as rheumatic diseases, asthma, risk factors of atherosclerosis, diabetes, ischemia-reperfusion, septic shock and many others. These evidences promote that assessment of bioactive PGF_2α and F₂-isoprostanes simultaneously in body fluids offers unique non-invasive analytical opportunity to study the function of these eicosanoids in physiology, oxidative stress-related and inflammatory diseases, and also in the determination of potency of various radical scavengers, anti-inflammatory compounds, drugs, antioxidants and diet.     

Doses of prostaglandin F2α effective for induction of parturition in goats

Twelve mixed breed does were injected with different doses of prostaglandin F₂α (PGF₂α) or saline on day 144 of gestation. Four each received single intramuscular injections of 5.0 or 2.5 mg PGF_2α, or 1.0 ml saline (controls). Systemic progesterone (P₄) concentrations were determined daily from day 144 until the day of kidding. Does receiving 5.0 mg PGF₂α, 2.5 mg PGF₂α, or saline kidded within mean (± SD) hours and range (hours) of 35 ± 8.6 and 28–48, 43 ± 11.8 and 29–57, and 111 ± 79.1 and 41–200, respectively. Mean (± SD) concentrations of P₄ (ng/ml) on the day of injection and on day 1 postinjection were 5.2 ± 2.6 and 0.7 ± 0.9, 5.3 ± 2.2 and 1.1 ± 1.0, and 6.4 ± 3.9 and 4.1 ± 2.6 for does receiving 5.0 mg PGF₂α, 2.5 mg PGF₂α, or saline, respectively. It was concluded that 5.0 mg and 2.5 mg PGF₂α effectively shortened the interval from injection to parturition, but that this interval was not as predictable as that previously reported with 20 mg PGF₂α.     

Coupling between cyclooxygenases and prostaglandin F2α synthase: Detection of an inducible,glutathione-activated,membrane-bound prostaglandin F2α-synthetic activity

Distinct functional coupling between cyclooxygenases (COXs) and specific terminal prostanoid synthases leads to phase-specific production of particular prostaglandins (PGs). In this study, we examined the coupling between COX isozymes and PGF synthase (PGFS). Co-transfection of COXs with PGFS-I belonging to the aldo-keto reductase family into HEK293 cells resulted in increased production of PGF_2α only when a high concentration of exogenous arachidonic acid (AA) was supplied. However, this enzyme failed to produce PGF_2α from endogenous AA, even though significant increase in PGF_2α production occurred in cells transfected with COX-2 alone. This poor COX/PGFS-I coupling was likely to arise from their distinct subcellular localization. Measurement of PGF_2α-synthetic enzyme activity in homogenates of several cells revealed another type of PGFS activity that was membrane-bound, glutathione (GSH)-activated, and stimulus-inducible. In vivo, membrane-bound PGFS activity was elevated in the lung of lipopolysaccharide-treated mice. Taken together, our results suggest the presence of a novel, membrane-associated form of PGFS that is stimulus-inducible and is likely to be preferentially coupled with COX-2.     

Antiluteogenic effects of serial prostaglandin F2α administration in cycling mares

A single dose of PGF2α does not consistently induce luteolysis in the equine CL until at least 5 days after ovulation, leading to the erroneous assumption that the early CL is refractory to the luteolytic effects of PGF2α. We hypothesized that serial administration of PGF2α in early diestrus would induce a return to estrus similar to mares treated with a single injection in mid-diestrus, and fertility of the induced estrus would not differ. The objectives of the study were to evaluate the effects of the 2 approaches as reflected by: (1) concentrations of plasma progesterone; (2) interovulatory and treatment-to-ovulation intervals; (3) the proportion of mares pregnant after artificial insemination. The study consisted of a balanced crossover design in which 10 reproductively normal Quarter Horse Mares were exposed to 2 treatments on 2 consecutive reproductive cycles. At detected ovulation (Day 0), mares were randomly allotted to 1 of 2 treatment groups: I, mid-diestrus treatment, administration of a single 10-mg dose of dinoprost tromethamine (PGF2α) im on Day 10; II, early diestrus treatment, administration of 10-mg PGF2α im twice daily on Days 0, 1, and 2 and once daily on Days 3 and 4. Mares in estrus and with a follicle 35 mm or greater in diameter were artificially inseminated with at least 2 billion motile sperm from a fertile stallion. Pregnancy was defined as detection of a growing embryonic vesicle on 2 consecutive examinations approximately 14 days after ovulation. Serial plasma samples were collected throughout the study period, and concentration of plasma progesterone was determined by RIA. A mixed-model ANOVA for repeated measures was used to analyze hormonal data. Interovulatory and treatment-to-ovulation intervals were compared by a paired t test and fertility by a McNemar chi-square analysis. All mares in group I underwent luteolysis after PGF2α administration denoted by mean (±SD) concentration of plasma progesterone of 0.25 ± 0.21 ng/mL detected 2 days after treatment. In group II, mean concentration of plasma progesterone remained below 1.0 ng/mL during treatment and until the onset of the next estrus. The mean interovulatory interval in group I was 18.5 ± 2.0 days compared with 13.1 ± 3.7 days in group II (P < 0.01). Treatment-to-ovulation intervals were 8.5 ± 2.0 days and 13.1 ± 3.7 days for groups I and II, respectively (P < 0.05). In both groups, 9 of 10 mares were pregnant (P = 1.0). Serial PGF2α administration beginning at ovulation consistently prevented luteal function in 10 of 10 mares in the present study without adversely affecting pregnancy rate of post-treatment cycles.     

Effect of prostaglandin F2α on anterior pituitary function in man

Five healthy adult men received iv PGF_2α at dosages of 0.05, 0.20 and 2.0 μg/kg/min for 30 min. There were no significant changes in serum FSH, LH or TSH levels. Serum GH and cortisol levels were slightly increased at the highest dosage. These responses were associated with, and presumably a result of, stressful side effects. Thus, PGF_2α cannot be used as a provocative test of pituitary hormone reserve.Prostaglandins (PG's) have recently been implicated in the release of a number of hormones from the anterior pituitary gland. The stimulation of GH release by PG's of the E series from incubated rat pituitary slices has been demonstrated. $\text{In vivo}$ stimulation by PGE₁ of ACTH in rats and of GH release in man has also been shown.The present study was undertaken in order to examine the efficacy of iv administration of PGF_2α as a provocative test of anterior pituitary hormone reserve in man. The responses in circulating levels of gonadotropins, TSH, GH, and cortisol (as an index of ACTH) were measured.     

Physiologic and nonphysiologic effects of exogenous prostaglandin F2α on reproductive hormones in mares

Responses to intravenous treatment of mares with prostaglandin F2α (PGF) 8 d after ovulation were studied in three groups (n = 4/group): control (no treatment), bolus (single treatment with 2.5 mg PGF), and infusion (0.1 mg PGF during 2 h). Infusion resulted in a 13,14-dihydro-15-keto-PGF2α (PGFM) concentration (559 ± 44 pg/mL) that was not different from the mean concentration for the major portion of a natural PGFM pulse associated with luteolysis (569 ± 45 pg/mL; n = 5). Progesterone in the bolus group increased (P < 0.03) between 0 (17.8 ± 3.5 ng/mL) and 2 min (25.3 ± 4.8 ng/mL), peaked at 10 min (28.5 ± 4.6 ng/mL), and then decreased. In the infusion group, progesterone decreased (P < 0.05) during 1 min (17.2 ± 1.3 ng/mL) to 15 min (13.5 ± 1.5 ng/mL) after the beginning of infusion and decreased (P < 0.05) similarly to the bolus group during 2 to 12 h; concentrations were lower (P < 0.05) at each hour than in controls. Interval between ovulations was shorter (P < 0.05) in the bolus (19.3 ± 2.0 d) and infusion (18.8 ± 2.1 d) groups than in controls (24.3 ± 1.3 d). Concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and cortisol increased (P < 0.05) within 10 min in the bolus group but did not change in the infusion group. Results supported the hypothesis that increases in progesterone, FSH, LH, and cortisol after a bolus luteolytic PGF treatment are nonphysiologic. Past conclusions on the nature of the luteolytic mechanism are problematic if based on responses to treatment with a single luteolytic bolus of PGF.     

Comparison of various semen extenders and addition of prostaglandin F2α on pregnancy rate in cows

This investigation comprises three trials. Trial 1 consists of an in vitro comparison of three semen extenders: two egg yolk based (customized Tris-egg yolk-glycerol and Triladyl®), the third (AndroMed®) soybean lecithin based. With regard to post-thaw motility, the phytoextender AndroMed® proved to be superior (59±3% v. 53±2% and 53±2%, P<0.05). It had earlier been shown that addition of the commercial prostaglandin F_2α preparation Dinolytic® before freezing compromises post-thaw motility; therefore, in Trial 2, Dinolytic® was added after thawing. Frozen-thawed spermatozoa tolerated addition of Dinolytic® at a concentration of 30% (v/v). In Trial 3, cows were inseminated using straws in which diluted semen and Dinolytic® were frozen in the same straw, separated by an air bubble, so intermingling could only take place in the course of insemination. Pregnancy rates at Dinolytic® dosages of 0%, 30% or 60% amounted to 44%, 41% and 56%, respectively (P>0.05), a result that encourages a large-scale field study, which is envisioned.     

Pulses of prolactin before, during, and after luteolysis and synchrony with pulses of a metabolite of prostaglandin F2α in heifers

Pulses of prolactin (PRL) and a metabolite of prostaglandin F2α (PGFM) were determined from hourly blood samples collected before, during, and after luteolysis (n=7 heifers). Progesterone concentrations were used to partition the results into six 12-h sets from 12h before to 36h after luteolysis. Pulses of PRL with a nadir-to-nadir interval of 4.4±0.2h were detected in each 12-h set. Pulses were rhythmic (P<0.05) in six heifers, beginning 12h before the end of luteolysis. The peak of a PRL pulse was greater (P<0.05) for the 12h after the end of luteolysis than for other 12-h sets, except for the last set of luteolysis. Area under the curve of a pulse was greater (P<0.05) for the 24h that encompassed the end of luteolysis than for two previous 12-h sets. Synchrony between the peaks of PRL and PGFM pulses was greater (P<0.03) during and after luteolysis (same hour for 29/39 pairs) than before luteolysis (0/12). Concentration of PRL centralized to the peak (Hour 0) of PGFM pulses was greater (P<0.05) at Hours 0 and 1 than at Hours -2, -1, and 3. Results supported the hypothesis that PRL is secreted in pulses in heifers. The pulses were most prominent and rhythmic during the last 12h of luteolysis and thereafter. The pulse peaks of PRL and PGFM were synchronized for most PRL pulses during and after luteolysis.     

Pregnancy termination by prostaglandin F2α stimulates maternal behavior in the rat

Treatment with PGF_2α resulted in the termination of pregnancy in 16- and 19-day pregnant rats, but not in 10- or 13-day pregnant rats. Rats that aborted displayed a rapid onset of maternal behavior when tested with foster pups. Aborted rats also displayed sexual receptivity and ovulation: these phenomena resemble the sequence of events following hysterectomy on the same days of pregnancy. Both can be related to the events surrounding normal parturition in the rat. The results are interpreted as due to a pregnancy-induced deactivation of the factor in the uterus that prevents estrogen from stimulating maternal behavior in nonpregnant females. In the absence of this factor, the PGF_2α-induced rise in estrogen secretion facilitates maternal behavior and sexual behavior and induces ovulation.