Effect of naloxone administration upon the diurnal concentrations of oxytocin in the cerebrospinal fluid of rhesus and cynomolgus monkeys.

A diurnal pattern in oxytocin concentrations is present in cerebrospinal fluid (CSF) removed from the spinal subarachnoid space of monkeys, with elevated levels occurring in the early light hours. In order to investigate the possible role of endogenous opioid peptides in the generation of this oxytocin rhythm, we administered naloxone (0.4 mg/kg/h x 48 h) to rhesus and cynomolgus monkeys and examined the effects on the diurnal pattern of oxytocin in CSF collected from the lumbar subarachnoid spinal space. Monkeys maintained on jacket/tether/swivel systems and in a 12 h light: 12 h dark cycle (lights on 07.00-19.00 h) were implanted with temporary spinal subarachnoid catheters. CSF was continuously collected from the lumbar subarachnoid space and assayed for oxytocin. Oxytocin concentrations in CSF showed a diurnal variation with peak and nadir concentrations during light and dark hours, respectively. The lumbar CSF concentrations of oxytocin were not significantly different during naloxone vs. saline infusion. Plasma oxytocin concentrations, measured in the same animals, displayed no diurnal variation and were not significantly different during naloxone vs. saline infusion. We conclude that naloxone administration for 48 h does not perturb the diurnal variation in oxytocin concentrations in the CSF of monkeys. Mu opioid receptors are unlikely to be involved in modulating the diurnal rhythm of oxytocin in the CSF of monkeys.     

Function and lifespan of corpora lutea in ewes treated with exogenous oxytocin

Oxytocin was administered to Dorset and Shropshire ewes in one experiment and to Dorset ewes in a further 4 experiments. In Exp. 1, concentrations of plasma progesterone and lengths of the oestrous cycle in ewes given oxytocin subcutaneously twice a day on Days 0-3, 2-5, 4-7, 6-9, 8-11, 10-13, 12-15 or 14-17 were similar to those of control ewes. In Exp. 2, intraluteal infusions of oxytocin from Day 2 to Day 9 after oestrus had no effect on concentration of progesterone, weight of CL collected on Day 9 or length of the oestrous cycle. In Exp. 3, intraluteal infusions of oxytocin on Days 10-15 after oestrus had no effect on weight of CL collected on Day 15. In Exp. 4, s.c. injections of oxytocin on Days 3-6 after oestrus had no effect on weight of CL collected on Day 9, concentrations of progesterone or length of the oestrous cycle. In Exp. 5, s.c. injections of oxytocin twice a day did not affect the maintenance and outcome of pregnancy in lactating and nonlactating ewes. Exogenous oxytocin, therefore, does not appear to affect luteal function at any stage of the ovine oestrous cycle although oxytocin has been reported by others to alter ovine CL function.     

Oestrogenic effects of ICI 182,780, a putative anti-oestrogen,on the secretion of oxytocin and prostaglandin F2α during oestrous cycle in the intact ewe

The effect of ICI 182,780, oestrogen antagonist, on the concentrations of oxytocin and uterine PGF_2α 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 F_2α, 15-keto-13,14-dihydro-prostaglandin F_2α, (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 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 (pg/ml)τ) 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 a 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 F_2α release in intact ewes when administered at 1.5 mg/kg/day over Day 13 to 15 post-oestrus.     

Pulsatile release of oxytocin into the circulation of the ewe during oestrus, mating and the early luteal phase

Two experiments were designed to investigate release patterns of oxytocin into plasma during oestrus and the early luteal phase. In Exp. 1, blood samples were collected from 5 ewes every 30 min for 10 h during 6 days around oestrus and the early luteal phase. During oestrus concentrations of oxytocin were generally low (1.27 +/- 0.54 pg/ml; mean +/- s.d.) but with occasional pulses up to 6 pg/ml. By Day 5 mean basal concentrations had risen to 4.5 +/- 2.1 pg/ml with a fluctuating release pattern. In Exp. 2, a method was developed for continuous blood sampling from conscious, unrestrained ewes. On the predicted day of oestrus following an untreated oestrous cycle, 8-ml blood samples were collected every minute for two 35-min periods (8 ewes: 16 sampling periods). For 6 ewes a ram was introduced to the pen for part of this time, and resulting behaviour was recorded. Additional blood samples were assayed for LH and progesterone to determine the stage of the cycle. Overall mean oxytocin concentrations ranged from 1.5 +/- 0.53 to 6.8 +/- 5.25 pg/ml in different animals. Ewes which were both in oestrus and exposed to the ram showed a pulsatile oxytocin release pattern consisting of low baseline concentrations with short-duration pulses superimposed (duration 1-4 min; amplitude 2.5-31.7 pg/ml; frequency 3.18/h). Coitus was not temporally associated with pulsatile release. However, the importance of the presence of the ram was indicated by total separation of 2 oestrous ewes from the ram until after experimentation. In these animals only 1 pulse of oxytocin was detected in 2.7 h of sampling. It is concluded that, although mean oxytocin concentrations at oestrus were low, short duration pulses were released into the plasma at this time. This effect may be dependent on the presence of a ram.     

Effect of post-mating GnRH analogue (buserelin) treatment on PGF2alpha release in ewes and ewe lambs

The objectives of this study were to determine the effects of buserelin or saline treatment on ovarian function (Experiment 1), plasma PGFM concentrations and oxytocin stimulated prostaglandin F(2alpha) (PGF(2alpha)) release (Experiment 2) in ewe lambs and ewes. Welsh Halfbred ewes (n=26) and ewe lambs (n=24) were mated to vasectomised rams at synchronised oestrus and on Day 12 post-mating each animal was injected intramuscularly either normal saline or 4 microg buserelin. In Experiment 1, plasma progesterone and oestradiol concentrations were determined in samples collected by jugular venepuncture 1h before and at 0, 2, 4, 6, 8, 24, 48 and 72 h after treatment (n=7 per treatment group). Progesterone concentrations increased (P<0.05) from 2 to 8h after buserelin treatment and returned to basal levels after 72 h, whereas oestradiol concentrations were maximal at 2h post-treatment and returned to basal levels after 24h (P<0.05). Oestradiol concentrations were lower (P<0.05) in buserelin-treated animals than controls at 72 h post-treatment. Basal and post-treatment progesterone concentrations were greater (P<0.05) in ewes than in ewe lambs but oestradiol levels were similar for both age groups. Ovulation rate, determined by laparoscopy on Day 14, was similar for both age groups (ewes 1.1; ewe lambs 1.0). Buserelin treatment induced accessory corpora lutea in ewes (4/7; 57%) but not in ewe lambs (0/7; 0%). In the Experiment 2, plasma PGFM concentrations were determined in samples collected at 20-min intervals for 6h on Day 14 and at 20-min intervals for 1h before and at 10-min intervals for 1h and then at 20-min intervals for a further 3h period after an intravenous injection of oxytocin (1IU/kg body weight) on Day 15 post-oestrus. In this experiment there were five ewe lambs and six ewes per treatment group. There was no effect of buserelin treatment or age on basal PGFM concentrations on either Day 14 or 15. Although peak PGFM concentrations tended to be lower in buserelin-treated animals, the difference was not significant (P>0.05). However, peak duration following oxytocin challenge on Day 15 post-mating was shorter (P<0.05) in control ewes compared with control ewe lambs. In conclusion, buserelin treatment given on Day 12 post-oestrus enhances luteal function more in ewes than ewe lambs and after a transitory increase, reduces oestradiol concentrations in both ewes and ewe lambs. However, buserelin treatment does not significantly attenuate the luteolytic signal.     

Hormonal changes during luteal regression in farmed fallow deer, Dama dama

Concentrations of progesterone, oxytocin and PGFM (pulmonary metabolite of PGF-2 alpha) were measured in plasma from peripheral blood samples collected from 5 fallow does every hour or 2 h for 12-h periods on Days 15-20 inclusive of the oestrous cycle (i.e. luteolysis). For 3 does that exhibited oestrus on Day 21, plasma progesterone concentrations fluctuated between 3 and 10 ng/ml on Days 15-18 inclusive. Thereafter, values declined progressively to attain minimum concentrations of less than 0.05 ng/ml on Day 20. Basal concentrations of plasma oxytocin and PGFM fluctuated between 5 and 20 pg/ml and 10 and 100 pg/ml respectively. Episodic pulses of plasma oxytocin (greater than 300 pg/ml) occurred on Days 15 and 16, whereas pulses of plasma PGFM (greater than 400 pg/ml) occurred on Days 19 and 20. There was little apparent correlation between episodic pulses of the two hormones. For 2 does that exhibited oestrus on Day 22, plasma progesterone concentrations declined to minimum values of 1.0-1.5 ng/ml by Day 20. One of these does showed very high levels of oxytocin secretion throughout the sampling period while the other showed an apparent paucity of oxytocin secretory periods. Two does hysterectomized on Day 13 of their second oestrous cycle failed to exhibit further oestrous cycles. Continual elevation of plasma progesterone concentrations (2-6 ng/ml) for an 8-month period indicated persistence of the corpus luteum after hysterectomy. It is concluded that luteolysis in fallow deer involves episodic secretion of both oxytocin and PGF-2 alpha.     

Central action of insulin regulates pulsatile luteinizing hormone secretion in the diabetic sheep model

This study tested the hypothesis that central mechanisms regulating luteinizing hormone (LH) secretion are responsive to insulin. Our approach was to infuse insulin into the lateral ventricle of six streptozotocin-induced diabetic sheep in an amount that is normally present in the CSF when LH secretion is maintained by peripheral insulin administration. In the first experiment, we monitored cerebrospinal fluid (CSF) insulin concentrations every 3-5 h in four diabetic sheep given insulin by peripheral injection (30 IU). The insulin concentration in the CSF was increased after insulin injection, and there was a positive relationship between CSF and plasma concentrations of insulin (r = 0.80, P < 0.01). In the second experiment, peripheral insulin administration was discontinued, and the sheep received either an intracerebroventricular (i.c.v.) infusion of insulin (12 mU/day in 2.4 ml saline) or saline (2.4 ml/day) for 5 days (n = 6) in a crossover design. The dose of insulin (i.c.v.) was calculated to approximate the increase in CSF insulin concentration found after peripheral insulin treatment. To monitor LH secretory patterns, blood samples were collected by jugular venipuncture at 10-min intervals for 4 h on the day before and 5 days after the start of i.c.v. insulin infusion. To monitor the increase in CSF insulin concentrations, a single CSF sample was collected one and four days after the start of the central infusion. The i.c.v. insulin infusion increased CSF insulin concentrations above those in saline-treated animals (P < 0.05) and maintained them at or above the peak levels achieved after peripheral insulin treatment. Central insulin infusion did not affect peripheral (plasma) insulin or glucose concentrations. LH pulse frequency in insulin-treated animals was greater than that in saline-treated animals (3.5 +/- 0.2 vs. 2.3 +/- 0.3 pulses/4 h, P < 0.01), but it was less than that during peripheral insulin treatment (4.8 +/- 0.2 pulses/4 h, P < 0.01). Our findings suggest that physiologic levels of central insulin supplementation are able to increase pulsatile LH secretion in diabetic sheep with low peripheral insulin. These results are consistent with the notion that central insulin plays a role in regulating pulsatile GnRH secretion.     

Effect of haloperidol, suckling, oxytocin and hand milking on plasma relaxin and prolactin concentrations in cyclic and lactating pigs

Prolactin secretion was stimulated in 5 cyclic gilts during the luteal phase (Day 10-13) with 5 mg haloperidol given i.v. Stimulation of prolactin secretion was also attempted by inducing milk let-down by suckling (4 sows), or by the injection of 1 mg oxytocin i.v. followed by hand milking (3 sows). Plasma prolactin concentrations increased significantly 1-2 h after haloperidol injection, and in 3 of 4 sows during suckling (P = 0.001); plasma relaxin concentrations did not change significantly at these times. No change was observed in plasma prolactin or relaxin concentrations at 15 min or 1-2 h after oxytocin injection and hand milking. Plasma relaxin concentrations ranged from below the sensitivity of the assay (100 pg/ml) to 450 pg/ml in lactating sows and from 100 to 2000 pg/ml in cyclic gilts. The results suggest that in cyclic gilts treated in the luteal phase with a dopaminergic receptor blocker, and in lactating sows during suckling, elevations in plasma prolactin concentrations were not accompanied, during the same period, by detectable changes in relaxin concentrations.     

Evidence for an oscillator other than luteinizing hormone controlling the secretion of progesterone in cattle

The objective of this study was to quantify and compare the frequencies of pulses in ovarian and systemic concentrations of progesterone, systemic concentrations of luteinizing hormone (LH) and rate of ovarian blood flow. Blood was collected simultaneously from previously implanted catheters in the ovarian venous circulation and jugular vein on Day 12 or 13 of estrous cycles from 4 nonlactating dairy cows. Blood was collected at a rate of 2.5 ml/min for 5 min out of every 10 min over an 8-h period. The mean rate of blood flow in the ovarian artery during the 5-min collection period was estimated by an electromagnetic blood flow transducer. Pulses were observed over time in both ovarian and systemic concentrations of progesterone at frequencies that ranged between 0.625 and 0.875 cycles/h (1.1 to 1.5 h/cycle) among the animals. Only one or two episodes of release of LH were observed during the 8-h period, and transient increases in blood flow to the ovaries were associated temporally with each episode of LH release. The estimated frequencies for release of LH and increased blood flow were the same for each animal and ranged between 0.250 and 0.375 cycles/h. A second cycle with a frequency similar to that for LH was evident in the spectral density functions for ovarian and systemic concentrations of progesterone. This cycle was eliminated when the cycle for LH was removed from the data for progesterone, but the magnitude and frequency of the pulses in progesterone were not affected.(ABSTRACT TRUNCATED AT 250 WORDS)     

Acute reduction in serum progesterone concentrations after feed intake in dairy cows

This study tested the hypothesis that high feed consumption will acutely decrease circulating progesterone concentrations. In the first experiment, a Latin Square design was used to test whether feeding pattern would alter circulating progesterone in pregnant lactating Holstein cows (n = 12). Feed was removed for 12h before the experiment and cows were then either fed 100% of the total mixed ration (TMR), 50% of TMR every 12h, 25% of TMR every 6h, or left unfed for an additional 12h. Blood samples were taken every hour for 24h. Provision of 100 or 50% of TMR decreased circulating progesterone by 1h after feeding and progesterone remained depressed until 8-9h after feeding. Feeding 25% of TMR did not reduce circulating progesterone concentrations. Experiment 2 used a crossover design to measure the effect of acute feeding on circulating progesterone and LH concentrations during delivery of a constant amount of exogenous progesterone (Eazi-Breed CIDRs) in lactating Holstein cows (n = 8) and nonpregnant dry Holstein cows (n = 6). Blood samples were taken every 15min for 8h. There was no change in serum progesterone during the 8h treatment period in unfed cows; however, feeding decreased (P<0.05) circulating progesterone between 2 and 6h after feeding. In lactating cows, feeding increased mean LH (P<0.05). There were more LH pulses (P = 0.01) in lactating than nonlactating cows. Thus, acute feeding reduced circulating progesterone in pregnant lactating cows apparently due to an increase in progesterone metabolism. Interestingly, feeding multiple smaller meals eliminated the acute effect of feeding on circulating progesterone.     

Oxytocin response to conditioned and nonconditioned stimuli in lactating ewes

We have measured oxytocin release during lactation in the ewe in response to normal tactile sucking stimuli as well as exteroceptive stimuli emanating from the lamb. Four puerperal ewes that had indwelling catheter inserted in the femoral artery while still pregnant were used. Each nursed a single lamb. Each was studied 2 or 3 times between Days 1 and 15 of lactation during a 2.5-h experimental period that was preceded by a 2-h separation from the lamb in the early morning. Samples were taken before and after the lamb was brought within sight and sound of the ewe but without contact, and then 0.5, 1, 5, 10, 15, 30, and 60 min after suckling began. When another suckling episode intervened, the same sampling schedule was immediately restarted. Suckling occurred in an intermittent fashion; 3 to 4 episodes of 2.9 +/- 2.0 (SD)-min duration took place with variable intervals during the 2.5-h experimental period. Exteroceptive stimuli emanating from the lamb caused plasma oxytocin to rise significantly from basal levels of 10.0 +/- 4.5 to 21.8 +/- 5.7 pg/ml (mean +/- SE, n 10, p less than 0.05). This rise was not seen on Day 1 and in only half of the ewes on Day 2, but thereafter the rise occurred in every instance. A further rise in plasma oxytocin was observed in almost all instances (86%) at suckling. Peak levels were usually observed within 1 min. They were quite variable, ranging from 15 pg/ml to 287 pg/ml, and not related to the milk yield, but were significantly greater than spontaneous pulses observed in nonlactating puerperal sheep.(ABSTRACT TRUNCATED AT 250 WORDS)     

Suppressed copulatory behavior and ovarian function in lactating Japanese monkeys (Macaca fuscata fuscata) during the mating season

The influence of lactation on copulatory behaviors and ovarian functions was studied in Japanese monkeys (Macaca fuscata fuscata) during the mating season. Three lactating females were housed in an outdoor group cage with their infants, and three nonlactating females were housed in an adjacent outdoor cage. They were mated by introduction of one of four rotationally chosen males into the females' cage, for two hours three times a week; the occurrence of ejaculatory copulations was recorded. Blood samples were collected on each observation day, and plasma levels of estradiol, progesterone, and luteinizing hormone (LH) were measured by specific radioimmunoassays. In nonlactating females, plasma estradiol increased during the transition into the mating season, and rose to levels over 90 pg/ml for the first time on about 50 days before the first ovulation. Shortly after plasma estradiol exceeded 90 pg/ml in the nonlactating females, the onset of ejaculatory copulations occurred. They received ejaculations continuously up to the early ovarian luteal phase. On the other hand, in lactating females, there were lower levels of plasma estradiol (below 90 pg/ml) during the transition into the mating season, and they received no ejaculation during that period. Two of the three lactating females ovulated only once, and they received ejaculations only during the periovulatory period, coinciding with the rise of their plasma estradiol levels over 90 pg/ml. The remaining lactating female remained anovulatory and received no ejaculation throughout the entire mating season. These results have demonstrated that the low sexual activity of lactating females is clearly correlated with low levels of plasma estradiol due to suppressed ovarian function.     

Dynamics of prostaglandin secretion, intrauterine fluid and uterine clearance in reproductively normal mares and mares with delayed uterine clearance

Two experiments were performed to investigate relationships between oxytocin, prostaglandin release, uterine emptying and fluid accumulation in the uterus. In Experiment 1, the effect of oxytocin on the pattern of prostaglandin release during uterine clearance of radiocolloid was measured in 5 normal mares and 5 mares with delayed uterine clearance. Uterine clearance was measured during estrus by scintigraphy at 0, 60 and 120 min after colloid infusion. After the 120-min reading, 20 IU, i.v., oxytocin were given, and the amount of colloid cleared was measured at 135, 150 and 180 min. Plasma was obtained prior to and during scintigraphy at 5- and 15-min intervals to measure concentrations of 15-keto-13,14-dihydro-PGF2 alpha metabolite (PGFM) by RIA. In Experiment 2, plasma PGFM levels were compared after administration of oxytocin in 8 normal mares and 6 mares with delayed uterine clearance to determine if intrauterine fluid stimulated prostaglandin release. Mares received 2 treatments in a cross-over design. Treatment 1 consisted of 20 IU, i.v., oxytocin during estrus. Treatment 2 consisted of an infusion of 10 mL, i.u., saline 15 min prior to oxytocin administration. Treatments were performed 4 to 6 h apart. Blood was collected and PGFM was measured as in experiment 1. Data were analyzed by least squares analysis of variance. In Experiment 1, regression analysis of scintigraphy and PGFM profiles indicated that time response curves differed between groups (P < 0.01). At 120 min, normal mares retained 40.4 +/- 4.9% (mean +/- SEM) of the radiocolloid while mares with delayed clearance retained 88 +/- 5%. Fifteen minutes after oxytocin administration (135 min), all normal mares and 4 of 5 mares with delayed clearance retained only < 6% of the colloid. During the first 120 min, plasma PGFM concentrations did not differ between the 2 groups. After oxytocin was given, plasma PGFM concentrations increased in 4 of 5 mares with delayed uterine clearance (80 to 3,096 pg/mL) but not in normal mares (13 to 46 pg/mL). In Experiment 2, plasma PGFM concentrations did not rise in normal mares but rose in 3 of 6 mares with delayed clearance (135 to 483 pg/mL) independent of treatment or period. The results suggest that intrauterine clearance of radiocolloid after oxytocin administration appears to be independent of PGF2 alpha release in normal mares during estrus. The difference in prostaglandin release response after oxytocin administration between the 2 groups was unrelated to the presence of intrauterine fluid.     

Effect of continuous infusion of oxytocin on length of the oestrous cycle and luteolysis in cattle

In Exp. I oxytocin (60 micrograms/100 kg/day) was infused into the jugular vein of 3 heifers on Days 14-22, 15-18 and 16-19 of the oestrous cycle respectively. In Exp. II 5 heifers were infused with 12 micrograms oxytocin/100 kg/day from Day 15 of the oestrous cycle until clear signs of oestrus. Blood samples were taken from the contralateral jugular vein at 2-h intervals from the start of the infusion. The oestrous cycle before and after treatment served as the controls for each animal. Blood samples were taken less frequently during the control cycles. In Exp. III 3 heifers were infused with 12 micrograms oxytocin/100 kg/day for 50 h before expected oestrus and slaughtered 30-40 min after the end of infusion for determination of oxytocin receptor amounts in the endometrium. Three other heifers slaughtered at the same days of the cycle served as controls. Peripheral concentrations of oxytocin during infusion ranged between 155 and 641 pg/ml in Exp. I and 18 and 25 pg/ml in Exp. II. In 4 our of 8 heifers of Exps I and II, one high pulse of 15-keto-13,14-dihydro-prostaglandin F-2 alpha (PGFM) appeared soon after the start of oxytocin infusion followed by some irregular pulses. The first PGFM pulse was accompanied by a transient (10-14 h) decrease of blood progesterone concentration. High regular pulses of PGFM in all heifers examined were measured between Days 17 and 19 during spontaneous luteolysis. No change in length of the oestrous cycle or secretion patterns of progesterone, PGFM and LH was observed.(ABSTRACT TRUNCATED AT 250 WORDS)     

Blood values of free-ranging patas monkeys (Erythrocebus patas)

Free-ranging patas monkeys (Erythrocebus patas) from El Guayacán island, Puerto Rico, were surveyed to establish values for the hemogram, serum biochemicals, calcium, and phosphorus. Results were tabulated for males and nonpregnant/nonlactating, pregnant, and lactating females. A summary of blood values from previous studies on captive patas monkeys was also tabulated for comparison.     

Effect of naloxone on plasma concentrations of prolactin and LH in lactating sows

Six lactating sows were injected through an indwelling vena cava cannula with naloxone (2.5 mg/kg body weight) on Day 15 post partum. Blood samples were collected through the cannulas at 10-min intervals for 8 h before and 10 h after naloxone administration. Plasma prolactin and LH concentrations were measured by radioimmunoassay. Naloxone caused a marked suppression of plasma prolactin concentrations lasting 4-6 h. LH concentrations were also affected by naloxone: LH rose to reach maximum values 20-50 min after naloxone treatment. Pretreatment values were recorded 200-300 min after the treatment. These results indicate that endogenous opioids are involved in causing the endocrine patterns occurring during lactation, i.e. high prolactin and low LH concentrations.     

HOMOVANILLIC ACID AND 3-METHOXY-4- HYDROXYPHENYLETHYLENEGLYCOL PRODUCTION BY THE MONKEY SPINAL CORD

The release of homovanillic acid (HVA) and 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG) into CSF by the monkey spinal cord was investigated with spinal subarachnoid perfusion of 20 rhesus monkeys. The preperfusion concentration of HVA in lumbar CSF was 365 ng/ml and in cisternal CSF was 365 ng/ml, while the concentrations of MHPG were 28.3 and 40.4 ng/ml respectively. HVA originating from the spinal cord appeared in the perfusate at a rate of 2.4 and MHPG at 1.4 ng/min. Treatment with probenecid either intraperitoneally or intrathecally did not alter the rate of release into CSF of these metabolites by the spinal cord but did significantly increase the rate of appearance in the cisterna magna of HVA originating from the brain. MHPG and HVA in lumbar CSF are therefore derived in part from spinal cord metabolism.     

The frequency of gonadotropin-releasing hormone secretion regulates expression of alpha and luteinizing hormone beta-subunit messenger ribonucleic acids in male rats

The influence of GnRH pulse frequency on LH subunit mRNA concentrations was examined in castrate, testosterone-replaced male rats. GnRH pulses (25 ng/pulse) or saline to controls, were given via a carotid cannula at intervals of 7.5-240 min for 48 h. alpha and LH beta mRNA concentrations were 109 +/- 23 and 30 +/- 5 pg cDNA bound/100 micrograms pituitary DNA, respectively, in saline controls. GnRH pulse intervals of 15, 30, and 60 min resulted in elevated alpha and LH beta mRNAs (P less than 0.01) and maximum responses (4-fold, alpha; 3-fold, LH beta) were seen after the 30-min pulses. Acute LH release to the last GnRH pulse was seen after the 15-, 30-, and 60-min pulse intervals. In contrast, LH subunit mRNAs were not increased and acute LH release was markedly impaired after the rapid (7.5 min) or slower (120 and 240 min) pulse intervals. Equalization of total GnRH dose/48 h using the 7.5- and 240-min intervals did not increase LH subunit mRNAs to levels produced by the optimal 30-min interval. These data indicate that the frequency of the pulsatile GnRH stimulus regulates expression of alpha and LH beta mRNAs in male rats. Further, GnRH pulse frequencies that increase subunit mRNA concentrations are associated with continuing LH responsiveness to GnRH.     

Effects of a luteolytic dose of oestradiol benzoate on uterine oxytocin receptor concentrations, phosphoinositide turnover and prostaglandin F-2 alpha secretion in sheep

Administration of oestradiol-17 beta benzoate on Days 9 and 10 of the oestrous cycle resulted in episodic secretion of PGF-2 alpha (as indicated by elevated circulating concentrations of 13,14-dihydro-15-ketoprostaglandin F-2 alpha) and a decline in circulating progesterone. Release of PGF-2 alpha began 35 +/- 3 h after first injection of oestrogen and progesterone concentrations declined from 42 +/- 3 h. Secretion of oxytocin, which was first observed 26 +/- 3 h after oestrogen treatment, preceded secretion of PGF-2 alpha; 69% of pulses of oxytocin coincided with episodes of PGF-2 alpha secretion. Uterine oxytocin receptor concentrations were raised in ewes treated with oestrogen, increases occurring in caruncular endometrium and myometrium by 12 h after treatment and in intercaruncular endometrium by 24 h. Raised receptor concentrations were followed at 24 h by increases in the incorporation of [3H]inositol into phosphatidylinositol and in the hydrolysis of labelled tissue phosphoinositides in response to oxytocin in slices of caruncular endometrium incubated in vitro. The following sequence of events is therefore suggested to occur at oestrogen-induced luteolysis: induction of the oxytocin receptor; increased turnover of phosphoinositides; onset of episodic secretion of PGF-2 alpha; and functional luteolysis.     

Effects of pregnancy and labor on oxytocin levels in human plasma and cerebrospinal fluid

In order to investigate the significance of oxytocin in pregnancy and labor, oxytocin concentrations in plasma and cerebrospinal fluid (CSF) were determined using the specific radioimmunoassay. Plasma and CSF samples were obtained from 23 pregnant women (11 pre labor, 12 in labor), 15 nonpregnant women and 4 men at spinal puncture for anesthesia. In males and nongravidas, CSF levels of oxytocin were significantly higher than plasma levels. Plasma levels in pregnant patients pre or in labor were significantly higher than those in nongravidas. No significant difference between CSF levels in prelabor gravidas (mean +/- SE, 9.7 +/- 1.5 mu u/ml) and nongravidas (10.1 +/- 1.2 mu u/ml) was found. However, CSF levels in gravidas in labor (18.6 +/- 2.3 micromicrons/ml were significantly higher than the levels in prelabor gravidas. These results strongly suggest that oxytocin levels in human plasma and CSF are controlled by different mechanisms and that the increased oxytocin could have some specific central actions.