Oxytocin and glucose oxidation in the rat uterus

The effects of oxytocin on the biochemical pathways of glucose oxidation were investigated in the rat uterus. In the presence of oxytocin, glucose oxidation in uterine segments obtained from Sprague-Dawley rats at diestrus increased 1.5–2.0-fold above the basal rate. A half-maximal response was observed at about 3 nM oxytocin; the maximum response was equal to or greater than the response to 1.7 nM insulin. In stripped myometrial segments (denuded of the endometrial component), oxytocin stimulated glucose oxidation at estrus only; whereas in intact uterine segments, the stimulation of oxidation was observed at both estrus and diestrus. In contrast, stimulation of oxidation by carbachol in stripped myometrial segments was independent of the estrous state of the tissue. The ratio of [1-¹⁴C]glucose to [6-¹⁴C]glucose oxidation was measured to estimate the relative involvement of the pentose phosphate and the tricarboxylic acid pathways of metabolism. In myometrial tissue, stimulation of glucose oxidation by oxytocin appeared to proceed through the tricarboxylic acid cycle. In intact uterine segments, at diestrus, glucose oxidation involved largely the pentose phosphate pathway (suggesting increased glucose metabolism in endometrial tissue), whereas at estrus, in the intact tissue segments, oxytocin increased glucose oxidation largely via the tricarboxylic acid cycle, and appeared to do so predominantly in the myometrial tissue. Carbachol-stimulated glucose oxidation appeared to proceed mainly via the tricarboxylic cycle in the myometrial tissue, irrespective of the stage of the estrous cycle. In the uterus of the Brattleboro rat (either intact uterine segments or stripped myometrial strips), oxytocin stimulated glucose oxidation only at estrus, predominantly through the tricarboxylic acid cycle. These findings suggest that oxytocin, in addition to its known effect on the contractility of uterine and myoepithelial smooth muscle, may regulate glucose metabolism in both the myometrial and endometrial components of uterine tissue.     

Mares with delayed uterine clearance have an intrinsic defect in myometrial function

Persistent, postmating endometritis affects approximately 15% of mares and results in reduced fertility and sizable economic losses to the horse-breeding industry. Mares that are susceptible to postmating endometritis have delayed uterine clearance associated with reduced uterine contractility. Unfortunately, the mechanism for reduced uterine contractility remains an enigma. The present study examined the hypothesis that mares with delayed uterine clearance have an intrinsic contractile defect of the myometrium. Myometrial contractility was evaluated in vitro by measuring isometric tension generated by longitudinal and circular uterine muscle strips in response to KCl, oxytocin, and prostaglandin F(2alpha) (PGF(2alpha)) for young nulliparous mares, older reproductively normal mares, and older mares with delayed uterine clearance. In addition, intracellular Ca(2+) regulation was evaluated using laser cytometry to measure oxytocin-stimulated intracellular Ca(2+) transients of myometrial cells loaded with a Ca(2+)-sensitive fluorescent dye, fluo-4. For all contractile agonists, myometrium from mares with delayed uterine clearance failed to generate as much tension as myometrium from older normal mares. Oxytocin-stimulated intracellular Ca(2+) transients were similar for myometrial cells from mares with delayed uterine clearance and from older normal mares, suggesting that the contractile defect did not result from altered regulation of intracellular Ca(2+) concentration. Furthermore, no apparent age-dependent decline was observed in myometrial contractility; KCl-depolarized and oxytocin-stimulated longitudinal myometrium from young normal mares and older normal mares generated similar responses. However, circular myometrium from young normal mares failed to generate as much tension as myometrium from older normal mares when stimulated with oxytocin or PGF(2alpha), suggesting possible age-related alterations in receptor-second messenger signaling mechanisms downstream of intracellular Ca(2+) release. In summary, for mares with delayed uterine clearance, an intrinsic contractile defect of the myometrium may contribute to reduced uterine contractility following breeding.     

Interaction of 4-hydroxylated estradiol and potential-sensitive Ca2+ channels in altering uterine blood flow during the estrous cycle and early pregnancy in gilts

This study was conducted to define further the role of catechol estrogens (CE) as intermediates in estrogen-stimulated uterine hyperemia. Previous studies from our laboratory strongly suggest that changes in uterine blood flow (UBF) result from alterations in uterine arterial tone (distensibility) and/or contractility (reactivity to alpha 1-adrenergic agonists). Tone changes appear to set the baseline rate of flow, whereas contractility changes result in short-term reductions in luminal diameter. Changes in uterine arterial tone and contractility result from alterations in Ca2+ uptake through potential-sensitive channels (PSCs) and receptor-operated channels (ROCs), respectively. Uterine and mesenteric arteries were removed from 6 gilts at estrus (Day 0), 9 gilts on Day 13 of gestation (high estrogen, high UBF), and 8 gilts on Day 13 of the estrous cycle (low estrogen, low UBF). Arterial measurements included initial tone (baseline perfusion pressure [BPP] to a constant intraluminal flow) and increased tone after exposure to KCl, the contractility in response to the alpha 1-agonist phenylephrine, and specific uptake of 45Ca before and after exposure to the CE 4-hydroxylated estradiol (4OH-E2). Contractility of uterine arteries from Day 13 nonpregnant (NP) and Day 13 pregnant (P) gilts to phenylephrine were similar and significantly greater (p less than 0.01) than contractility of vessels from estrous gilts. The BPP and responses of uterine arteries from Day 13 NP gilts to KCl were greater (p less than 0.05) than the BPP and responses of arteries from Day 13 P and estrous gilts, which were similar to each other.(ABSTRACT TRUNCATED AT 250 WORDS)     

An in vitro study on spontaneous myometrial contractility in the cow during estrus and diestrus

Myometrial smooth muscle strips were collected from slaughtered cows in estrus and diestrus. Longitudinal and circular smooth muscle strips were mounted in organ baths and after equilibration time and 2 g preload, their physiologic contractility was recorded for 3 h. Area under the curve (AUC), mean amplitude (MA) and frequency of contractions (F) were studied. Differences between cycle phases, between muscle layers and over the recorded time period were statistically evaluated. In the cow, physiologic contractility patterns (measured as AUC and MA) of circular versus longitudinal myometrial strips are always different during the 3 h recording. Significant differences between estrus versus diestrus are only found for circular layers, but not for longitudinal layers. Significant differences over time are only found for longitudinal layers.     

Hormonal variation of rat uterine contractile responsiveness to selective neurokinin receptor agonists

Regulated uterine contractions are important in many reproductive functions such as sperm transport and embryo positioning during implantation. The role of classical neurotransmitters including acetylcholine and norepinephrine in regulating myometrial contractility has been well studied; however, the peripheral role of sensory neurotransmitters such as the neurokinins is less clear. The major neurokinins are substance P, neurokinin A, and neurokinin B, which predominantly activate neurokinin receptors (NK-Rs) 1, 2, and 3, respectively. This study utilized selective receptor agonists to examine the role of NK-Rs in uterine contractility. Uterine tissues, obtained from the major stages of the rat estrous cycle, were stimulated with selective NK-R agonists. Addition of each agonist resulted in a significant contractile response. However, the magnitude and nature of the response were dependent upon the stage of the estrous cycle, with responses to all agonists being significantly decreased in tissue from proestrus and estrus. Furthermore, the nature of NK3-R-mediated contraction was different in tissue from proestrus and estrus compared to metestrus and diestrus. The hormonal dependence of NK-R-mediated contractility was then examined in the ovariectomized estrogen-supplemented rat model. These studies confirmed that the magnitude and nature of uterine contractility in response to NK-R activation depend upon the hormonal environment.     

Spinal effects of oxytocin on uterine motility in anesthetized rats

The rat uterus receives an innervation from the lumbosacral and thoracolumbar segments of the spinal cord. These segments receive descending oxytocinergic projections from the paraventricular nucleus of the hypothalamus. We tested the hypothesis that oxytocin regulates uterine motility through a spinal site of action. Oxytocin was administered in anesthetized female rats either intrathecally at the lumbosacral or thoracolumbar spinal cord levels or intravenously. Uterine activity was revealed by measuring changes of intrauterine pressure using an indwelling balloon placed in one caudal uterine horn. The uterus displayed a spontaneous activity characterized by intrauterine pressure rises, the frequency, amplitude, and duration of which were dependent on the stage of the estrous cycle. Oxytocin delivered at the lumbosacral level affected the frequency (during proestrus, estrus, and diestrus) and amplitude (during proestrus and estrus) of uterine activity. During estrus, oxytocin delivered at the thoracolumbar level affected the frequency, amplitude, and duration of the intrauterine pressure rises. Intravenous oxytocin not only affected intrauterine pressure rises (namely amplitude during proestrus and estrus and frequency and duration during estrus) but also increased the basal tone during estrus. The effects of lumbosacral oxytocin were partly mimicked by the oxytocin agonist [Thr(4),Gly(7)]-oxytocin blocked by the oxytocin receptor antagonist atosiban and by hexamethonium. Arginine vasopressin delivered at the lumbosacral level had no effect. These results support our hypothesis that oxytocin released by descending paraventriculo-spinal pathways and acting on spinal oxytocin receptors modulates the activity of the uterus. This regulation is cycle dependent.     

Changes in uterine secretion of prostaglandin F2 alpha and luteal secretion of progesterone in response to oxytocin during the porcine estrous cycle.

The purpose of this experiment was to determine whether the ability of oxytocin to stimulate uterine secretion of prostaglandin F2 alpha (PGF2 alpha) and luteal secretion of progesterone changes during the porcine estrous cycle. Nineteen multiparous sows were observed for estrus. After one estrous cycle of normal length, sows were assigned randomly to receive an injection of oxytocin (30 IU, i.v.) in the EARLY (Days 4-6; n = 6), MID (Days 9-11; n = 7), or LATE (Day 15; n = 6) stage of the estrous cycle. Concentrations of 13, 14-dihydro-15-keto-PGF2 alpha (PGFM) and progesterone were determined in jugular venous serum samples collected at -60, -45, -30, -15, 0, 2, 5, 10, 15, 30, 45, 60, 90, and 120 min after injection of oxytocin. The magnitudes of the PGFM and progesterone responses and the area under the respective response curves (AUC) were calculated for each sow. Concentrations of PGFM did not change in response to oxytocin administered during the EARLY or MID portions of the estrous cycle. Concentrations increased rapidly in 4 of 6 sows that received oxytocin LATE in the estrous cycle. Both magnitude and AUC were greater LATE in the estrous cycle than at either EARLY or MID cycle (p less than 0.05). Thus, uterine secretory responsiveness to oxytocin develops between Days 11 and 15 postestrus in the sow. For progesterone, a transient increase was observed immediately following injection of oxytocin at MID cycle (p less than 0.05), but not at the other times examined. Therefore, oxytocin appears to be capable of stimulating secretion of progesterone from the functionally mature corpus luteum.     

Uterine responsiveness of oxytocin and prostaglandin F2 alpha in heat-acclimated rats

1. Contractility, in vitro, was examined in uterine horns of rats acclimated to 35 degrees C and controls (22 degrees C). 2. Responses to oxytocin and prostaglandin F2 alpha were measured in the four stages of the estrus cycle and on day 4 of pregnancy. 3. Responses to oxytocin of uteri from heat acclimated rats were significantly depressed in estrus, metestrus and diestrus, while responses to prostaglandin F2 alpha were decreased in estrus and metestrus. 4. Responses to oxytocin and prostaglandin were slightly but insignificantly decreased in uteri from pregnant day 4 heat-acclimated rats.     

Decrease in activity of smooth muscle L-type Ca2+ channels and its reversal by NF-kappaB inhibitors in Crohn's colitis model

We investigated the mechanisms of dysmotility of the colonic circular muscle of the Crohn's disease rat model. Contractions induced by KCl, carbachol, and Bay K 8644 were decreased in circular smooth muscles isolated from 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis rat colon. However, the absolute force and Ca2+ sensitivity of contractile proteins were not affected as assessed in alpha-toxin permeabilized smooth muscle. The current density of the L-type Ca2+ channel in circular smooth muscle cells was significantly decreased in the TNBS-treated colonic cells. However, expressions of the L-type Ca2+ channel mRNA and protein did not differ between control and TNBS-treated preparations. Pretreatment with the NF-kappaB inhibitors pyrrolidinedithiocarbamate and sulfasalazine partially recovered the decreased contractility and current density of the L-type Ca2+ channel by TNBS treatment. These results suggest that the decrease in the contraction of circular smooth muscle isolated from TNBS-induced colitis rat colon, which may be related to gut dysmotility in Crohn's disease, is attributable to the decreased activity of the L-type Ca2+ channel. The dysfunction of the L-type Ca2+ channel may be mediated by NF-kappaB-dependent pathways.     

The ovarian and cervical regions of the rat uterus display a different contractile response to serotonin and prostaglandin F2alpha. I. The estrous cycle

In pharmacological studies using isolated tissues, the sensitivity to different agonists may vary depending on the anatomical region. The aim of the present study was to evaluate the in vitro contractile response to serotonin, prostaglandin F2alpha, and oxytocin of the ovarian and the cervical uterine segments isolated from rats in the four different stages of the rat estrous cycle. Non-cumulative curves were recorded for both, the ovarian and the cervical uterine segments. The cervical portion displayed a higher contractile response to serotonin and a lower response to PGF2alpha than the ovarian portion. Oxytocin induced similar responses in both uterine segments. The uterine ovarian segment displayed a similar sensitivity to serotonin in all the estrous cycle stages, whereas in the cervical segment, influenced by estrogens in diestrus and proestrus, an increase in contractility was observed. According to these findings, serotonin might participate in the spermatozoa transport toward the oviduct. The higher response of the ovarian portion to prostaglandin F2alpha is in line with its role during labor and delivery.     

Xylazine enhances porcine myometrial contractility in vitro: possible involvement of alpha 2-adrenoceptors and Ca2+ channels

The effects of xylazine on porcine myometrial contractility were studied in vitro using uterine strips to determine the alpha 2-adrenergic influences during the diestrous stage of the estrous cycle. Xylazine (10(-8)-10(-5) M) caused a dose-dependent increase in the amplitude of myometrial contractility. The alpha 2-adrenoceptor antagonists idazoxan and yohimbine (10(-8)-10(-6) M) blocked the effects of xylazine in a dose-dependent manner. Yohimbine was approximately 10 times more potent than idazoxan in this regard. In contrast, an alpha 1-adrenoceptor antagonist prazosin (10(-7) and 10(-6) M) did not block the xylazine-induced increase in myometrial contractility, but a higher dose of prazosin (10(-5) M) did reduce the effects of xylazine. When the porcine uterine strips were pretreated with Ca2(+)-free Tyrod's solution or verapamil, a Ca2+ channel blocker, the effects of xylazine on myometrial contractility were completely abolished, whereas those of carbachol were only moderately reduced. The results suggest that the xylazine-induced myometrial contractility is mediated by alpha 2-adrenoceptors and that this effect is mediated, at least in part, by Ca2+ channels, whereas the effect of carbachol is attributed to an increase in both Ca2+ entry and release of Ca2+ from intracellular pools.     

Circulating concentrations of oxytocin during the estrous cycle and early pregnancy in sheep

Plasma concentrations of oxytocin and progesterone have been measured by radioimmunoassay in jugular venous blood obtained daily from 5 sheep during 2 estrous cycles and in early pregnancy.Concentrations of oxytocin were relatively high (15–30 pg/ml) during the luteal phase of the cycle, but fell at estrus (to 1–17 pg/ml). A fall in oxytocin was also observed on day 15 of pregnancy, when, as expected, progesterone levels remained high. It is suggested that raised basal levels of oxytocin are unlikely to cause the increasing uterine release of prostaglandin F_2α which occurs at the end of the estrous cycle.     

Acute and chronic estrogen supplementation decreases uterine sympathetic innervation in ovariectomized adult virgin rats

Uterine innervation undergoes substantial reorganization associated with changes in reproductive status. Nerves innervating the uterus are decreased in pregnancy and puberty, and even the normal rodent estrous cycle is characterized by fluctuations in numbers of myometrial nerve fibers. During the follicular (proestrus/estrous) phase of the estrous cycle, intact nerves are rapidly depleted and then return over the next 2-3 days in the luteal (metestrus/diestrus) phase. We hypothesize that uterine nerve depletion is initiated by increased circulating estrogen in the follicular phase. However, studies have not shown whether estrogen can reduce uterine innervation and, if so, whether the time course is compatible with the rapid changes observed in the estrous cycle. These questions were addressed in the present study. Mature ovariectomized virgin rats received 17-beta-estradiol as a single injection (10 microg/kg s.c.) or chronically from timed-release pellets (0.1 microg/pellet for 3 weeks sustained release). Total (protein gene-product 9.5-immunoreactive) and sympathetic (dopamine beta-hydroxylase-immunoreactive) uterine innervation was assessed quantitatively. Both total and sympathetic innervation was abundant in uterine longitudinal smooth muscle of ovariectomized rats. However, following acute or chronic estrogen administration, total and sympathetic fiber numbers were markedly decreased. This was not due to altered uterine size, as reductions persisted after correcting for size differences. Our results indicate that sympathetic nerves are lost from uterine smooth muscle after estradiol treatment in a manner similar to that seen in the intact animal during estrus and pregnancy. This suggests that the rise in estradiol prior to estrus is sufficient to deplete uterine sympathetic innervation.     

Inhibitory effect of GnRH on isolated rat uterine muscle contractility

The effect of GnRH upon uterine contractions of both non-pregnant and pregnant rats was examined in vitro. In the non-pregnant rat uterus, GnRH inhibited in a concentration-and-time dependent manner the contractions induced by acetylcholine and oxytocin, but not those caused by bradykinin and angiotensin II. GnRH also inhibited the rhythmic contractions induced by oxytocin in uterine strips from late pregnant rats. These findings show that GnRH has a direct inhibitory effect on the rat uterine contractions, suggesting that GnRH-like substances may exert modulatory influences upon rat uterine contractility.     

Comparison of invivo and invitro uterine contractility in the ewe

Uterine contractions were observed $\text{in}$$\text{vivo}$ by laparotomy and exposure of the uterus. Ten hours after the beginning of estrus, an average of 39 contractions per 10 min originated in the posterior ends of the uterine horns and moved toward the oviducts, while an average of, 13 contractions originated in the anterior ends of the horns and moved toward the cervix. Two days later (58 hr after the beginning of estrus), the contractions had changed in origin and direction; only 6 contractions originated in the posterior ends of the horns and moved anteriorly, while 39 originated in the anterior ends and moved posteriorly.Experiments were done to determine whether the change in origin of contractions $\text{in}$$\text{vivo}$ was reflected in the contractility of strips of myometrium in a tissue bath. The number and amplitude of contractions were recorded from strips of circular and of longitudinal myometrium taken from the posterior and anterior ends of the uterine horns at 10 and 58 hr after the beginning of estrus. The myometrial strips contracted approximately 3 to 4 times per minute regardless of the time after the beginning of estrus, the end of the uterine horn from which the tissue was taken, or whether the contracting muscle was circular or longitudinal. Thus, the physiological mechanisms that controlled the number and origin of uterine contractions $\text{in}$$\text{vivo}$ did not maintain that control over myometrial tissue $\text{in}$$\text{vitro}$.     

Concentrations of 13, 14-dihydro-15-keto-prostaglandin F(2)alpha, estradiol-17beta and progesterone during the peripubertal period in heifers

Twenty prepubertal Holstein heifers were utilized to assess plasma 13, 14-dihydro-15-keto-prostaglandin F(2)alpha (PGFM), serum progesterone (P(4)) and estradiol-17beta (E(2)) concentrations as well as the E(2):P(4) ratio during the onset of puberty in cattle. All animals were maintained as a group along with a sterile marker bull to assist in the detection of estrus. Upon detection of the first estrus (Day=O), daily blood samples were collected from a jugular vein until the heifers had completed 3 estrous cycles. The average body weight and age at first estrus were 247.6+/-4.8 kg and 304.0+/-7.5 days, respectively. Frequency of abnormal length estrous cycles was greater (P<0.02) during the first (40%) and second (35%) cycles than during the third estrous cycle (0%). All heifers had normal cycle lengths (18 to 24 days) by the third estrous cycle. Serum P(4) was greater during the third cycle (P<0.05) from Day 10 to Day 4 before the next estrus compared with the same period of the first estrous cycle. Serum E(2) did not peak until the day of estrus in the first cycle, whereas E(2) reached a maximal level 2 days before estrus in the third estrous cycle. Serum E(2) was higher (P<0.0001) 2 days before estrus in the third cycle than in the first estrous cycle. Plasma PGFM reached maximum concentrations 3 days before estrus in the third cycle compared with 1 day before estrus at the end of first estrous cycle. As estrus approached during the third cycle, PGFM rose 1 day before E(2) rose and P(4) declined, while the rise in PGFM and E(2) occurred simultaneously, with P(4) declining at the end of the first estrous cycle. During diestrus, the E(2):P(4) ratio was lower (P<0.07) in the third cycle than in the first, but it was higher (P<0.04) at estrus and 1 day before in the third estrous cycle. These data reveal a high incidence of abnormal length estrous cycles during the first two estrous cycles of the peripubertal period, and demonstrate anomalies in uterine and ovarian endocrine activity during the peripubertal period in cattle.     

Luminal antioxidants enhance the effects of mesalamine in the treatment of chemically induced colitis in rats

Previous experiments in rats with chemically induced colitis have shown that the antioxidant N-acetylcysteine plus mesalamine (5-ASA) exerted a significantly greater therapeutic effect in promoting mucosal healing when compared to either agent alone. The aims of the present study were to compare the effects of three antioxidants plus mesalamine vs. 5-ASA alone in treatment of colitis induced by trinitrobenzene sulfonic acid (TNBS) in rats. Methods: Three days following induction of TNBS colitis, rats received 8 days of rectal therapy with 5-ASA, or 5-ASA plus vitamin C (ascorbic acid), 5-ASA plus phenyl butylnitrone (PBN) and 5-ASA plus vitamin E (alpha-tocopherol). Distal colonic tissues were examined for microscopic colitis and myeloperoxidase (MPO) activity. Results: Global assessments of microscopic colitis induced by TNBS indicated that 5-ASA alone significantly changed colonic injury by -31%. Combination therapy with ascorbic acid plus 5-ASA or alpha-tocopherol plus 5-ASA caused further significant change in TNBS colitis by -65 and -82%, respectively. Each of these values was significantly below scores observed with 5-ASA as monotherapy. Reduction in colitis with PBN plus 5-ASA was not different from 5-ASA alone. MPO activity was decreased significantly in response to monotherapy with 5-ASA and each of the antioxidants plus 5-ASA when compared to TNBS. alpha-Tocopherol plus 5-ASA, however, was the only treatment strategy that reduced significantly MPO activity below that recorded for 5-ASA alone. In conclusion, our results indicate that antioxidants other than N-acetylcysteine significantly enhance the therapeutic effectiveness of 5-ASA in the treatment of TNBS colitis. alpha-Tocopherol plus 5-ASA exerted profound anti-inflammatory and reparative effects upon colitis induced by TNBS.     

Oxytocin receptors and contractile response of the myometrium after long term infusion of prostaglandin F2 alpha, indomethacin, oxytocin and an oxytocin antagonist in rats

Binding of [3H]oxytocin to isolated myometrial plasma membranes was not affected by the presence of prostaglandin (PG)F2 alpha or E2 in the incubation medium. Long-term treatment with PGF2 alpha or indomethacin had no effect on oxytocin receptor concentrations and dissociation constants of myometrial plasma membranes nor on maximal contractility or KM values of isolated uterine strips exposed to oxytocin. Infusion of oxytocin for 5 days in non-pregnant rats resulted in a decrease in oxytocin receptor concentrations in myometrial plasma membranes whereas the binding affinity to oxytocin was unaffected. Isolated uterine strips from similarly treated rats showed a reduced maximal contractile response to oxytocin and an elevated KM value, possibly indicating an influence of oxytocin on the coupling between receptor occupancy and contractility. Treatment for 5 days with desamino1-[D-Tyr(O-ethyl)2-Thr4-Orn8] oxytocin (an oxytocin antagonist) increased the concentration of myometrial oxytocin receptors. In addition KD values of these receptors were elevated. The present results indicate that prolonged exposure to oxytocin leads to a down-regulation of the myometrial receptor concentration, which is not caused by ligand-receptor interaction in itself. The concerted effect of oxytocin and prostaglandins on myometrial contraction does not appear to involve modulation of the oxytocin receptor by prostaglandins.     

Delayed puberty and response to testosterone in a rat model of colitis

Delayed puberty is a frequent complication of inflammatory bowel disease. The precise etiological mechanisms are not known. In this study, we wanted to determine the relative contribution of undernutrition and inflammation to delayed puberty and the effect of inflammation on the reproductive axis. Puberty was assessed in rats with 2,4,6-trinitrobenzenesulfonic acid induced-colitis, healthy controls, and animals pair fed to match the food intake of the colitic group. The response to testosterone administration was assessed in colitic rats. We found that induction of colitis was associated with hypophagia and reduced weight gain, and undernutrition in healthy females (i.e., pair fed) resulted in a delay in the onset (by 4.8 days, P < 0.001) and progression of puberty (normal estrous cycles in 42%, P = 0.04) compared with controls. However, puberty was further delayed in the colitic group (1.4 days after pair fed) with the absence of normal estrous cycling in all rats. In males, the onset of puberty was also delayed, and weights of accessory sex organs were reduced compared with pair-fed controls. Plasma testosterone concentrations were low, and gonadotropin concentrations were normal in colitic rats. Testosterone treatment normalized puberty in male rats with colitis. In conclusion, in rats with experimental colitis, inflammation appears to potentiate the effect of undernutrition on puberty. The weights of secondary sex organs and the onset of puberty were normalized by testosterone treatment.     

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 radioimmunoassay 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 alpha-blocking agent, had no effect on the epinephrine-induced release of PGF, while propranolol, a beta-blocking agent, not only prevented in 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 PGF2alpha.