Plasma adrenocorticotropic hormone and cortisol in pigs: effects of time of day on basal and stressor-altered concentrations

An initial study was conducted to establish the presence in plasma of diurnal rhythms of immunoreactive porcine adrenocorticotropic hormone (pACTH) and cortisol in castrated male pigs (barrows). Fourteen barrows with jugular catheters were bled at 6-hr intervals for 24 hr. Significant changes in plasma pACTH were evident with peak levels (61 +/- 6 pg/ml) at 0100-0700 hr and a trough (38 +/- 4 pg/ml) at 1900 hr. Changes (P less than 0.05) in plasma cortisol were also present in barrows with a peak (44 +/- 6 ng/ml) at 0700 hr and a trough (21 +/- 5 ng/ml) at 1900 hr. Plasma norepinephrine and epinephrine were measured at the same time intervals and did not differ among hours. In these unstressed pigs the ratio cortisol/log10pACTH at 0700 hr (25.3 +/- 3.0) was greater than the ratio at 1900 hr (12.9 +/- 2.7). Sequential blood samples were subsequently taken on four of the barrows 12 and 26 days later. Plasma pACTH was variable among pigs and did not differ among hours. Plasma cortisol on both dates was greater (P less than 0.05) in the morning (0100 or 0700 hr) than at 1900 hr. The ratio cortisol/log10pACTH at 0700 hr was repeatedly greater than at 1900 hr. A second study was conducted to determine whether plasma pACTH and cortisol responses to mild (32 degrees C for 2 hr) or strong (20-min restraint) stressors were dependent on the time of day of stressor application (0800 hr, AM; 1600 hr, PM). Response-associated parameters (maximum concentration, maximum incremental concentration, and integrated response) for pACTH and cortisol did not differ between AM and PM. However, a qualitative difference existed between the AM and PM plasma pACTH responses to restraint +32 degrees C wherein the AM response consisted of a single prolonged surge, and the PM response of an initial major peak followed by a second significant minor peak. A suggested explanation is that the initial 20-min restraint stressor potentiated the hypothalamic-hypophyseal response to 32 degrees C. These studies are the first direct measurements which suggest the presence of diurnal changes in plasma ACTH and cortisol in barrows. The studies also indicate for barrows an absence of diurnal changes in plasma epinephrine and norepinephrine. The responsiveness of the pituitary-adrenocortical axis to stressors did not exhibit quantitative diurnal changes at the time periods measured. However, it is hypothesized that the repeatable AM-PM difference in the ratio cortisol/log10ACTH reflects a diurnal change in adrenal responsiveness to ACTH in unstressed pigs.     

Effect of calf removal on serum luteinizing hormone and cortisol concentrations in postpartum beef cows

Serum luteinizing hormone (LH) and cortisol concentrations were measured in ten fall calving, Angus cows averaging 38 +/- 8 days postpartum. Calves from five cows were weaned at the beginning of the study. Blood samples were collected at 20 min. intervals for 48 h after weaning and for 8 h on day 4 and day 6 postweaning. Mean serum LH concentrations increased (P<0.01) in weaned cows (W) from 0.55 +/- 0.01 ng/ml at time of calf removal to 1.3 +/- 0.04 ng/ml 48 h afterwards. Comparable LH concentrations for suckled cows (S) were 0.65 +/- 0.08 ng/ml and 0.62 +/- 0.03 ng/ml respectively. Average serum LH concentrations at 48 h after weaning were greater (P<0.01) for W cows than S cows and a treatment by time interaction occurred (P<0.01) with serum LH concentrations increasing (P<0.01) from time of calf removal to 48 h after calf removal in W cows. Frequency of LH peaks increased (P<0.01) in W cows and by 48 h after weaning was greater (P<0.01) in W cows than in S cows. Magnitude of LH peaks did not differ between the two groups. Serum cortisol concentrations were not different between W and S cows except for a transient elevation (P<0.01) in W cows from 7.6 +/- 0.9 ng/ml to 11.9 +/- 1.0 ng/ml 9 to 12 h after calf removal. Since serum LH concentrations were increased in W cows but not in S cows at 48 h and serum cortisol concentrations increased transiently in W cows we suggest that circulating cortisol levels may not be a physiological inhibitor of LH secretion in the suckled postpartum beef cow.     

Pituitary-adrenocortical and lymphocyte responses to bromocriptine-induced hypoprolactinemia, adrenocorticotropic hormone, and restraint in swine

A study was conducted with castrated male pigs (barrows) to evaluate effects of bromocriptine-induced hypoprolactinemia (6 days) on basal and adrenocorticotropic hormone (ACTH)-altered (single injection) pituitary-adrenocortical function, on lymphocyte proliferative responses, and on interleukin 2 production. In addition, the study was designed to measure the short time course of pituitary-adrenocortical and lymphocyte responses to ACTH and to a 30-min restraint stressor. Blood samples were taken via indwelling jugular catheters at -0.5, +0.5, +2, and +5 hr (with reference to time of acute treatment exposure) on Day 6 of the study. Lymphocyte responses were measured only at the 2-hr interval. Exposure (6 days) to bromocriptine (CB154) was associated with 53% reductions (P less than 0.05) in plasma prolactin (1.37 +/- 0.13 vs 0.60 +/- 0.04 vs 0.68 +/- 0.08 ng/ml) when averaged across all time intervals in control, CB154-treated, and CB154 + ACTH-treated pigs, respectively. The reductions in plasma prolactin were associated with a reduction (P less than 0.05) in basal plasma cortisol at only one time interval (+0.5 hr) when CB154-treated pigs were compared with controls (17.7 +/- 4.2 vs 26.9 +/- 3.2 ng/ml). CB154 had no effect on plasma ACTH or growth hormone concentrations for the time periods at which they were measured. CB154 treatment produced numerical, but not statistically significant, 38% reductions in interleukin 2 production (6.31 +/- 1.8 vs 3.91 +/- 1.47 units/ml). Lymphocyte proliferative responses to the mitogen concanavalin A and interleukin 2 production decreased 65 and 75% (P less than 0.05), respectively, 2 hr subsequent to ACTH administration when compared with control animals. Hence, under the conditions of this study, only a modest association between lowered plasma prolactin concentrations and basal cortisol concentrations was evident. The data suggest the absence of dopamine regulation of basal plasma ACTH in pigs and provide evidence for a rapidly occurring inhibitory effect of ACTH administration on specific lymphocyte activities.     

Effects of dietary energy level on luteinizing hormone and adrenal function in the post partum beef cow

The effects of dietary energy and suckling on adrenal function and luteinizing hormone (LH) concentrations were investigated in primiparous postpartum cows. Ten heifers were assigned at calving to either high (22.8 Mcal/day) or low (15.2 Mcal/day) energy diets. Blood samples were collected every 15 minutes for 8 hours on 28, 42, and 56 days post partum. Calves were allowed to suckle ad libitum during sampling periods. Serum samples were analyzed by radioimmunoassay for LH and cortisol. Concentrations of catecholamines were quantified by reverse-phase HPLC. Body weights were decreased (P<0.01) by low energy intake. In addition, low energy diet cows had lower mean LH concentrations (0.97 +/- 0.09 vs 1.57 +/- 0.07 ng/ml), P<0.05) than high energy diet cows. Luteinizing hormone concentrations in high energy diet cows increased with days post partum, resulting in a treatment-by-time interaction (P<0.005). Treatment did not affect mean cortisol concentrations. However, within 15 minutes of suckling cortisol release was significantly above baseline in 77% of the observed suckling events. Dihydroxyphenylalanine (DOPA) increased in high energy diet cows compared with that of low energy diet cows (2,833 +/- 243 vs 1,294 +/- 243 pg/ml, P<0.01). Norepinephrine (NE) and 3,4-dihydroxyphenylacetic acid (DOPAC) were not influenced by treatment. Plasma NE decreased during the postpartum interval (P<0.005). These data suggest that reduced energy intake may prevent the increase in LH associated with increasing days post partum and alter adrenal function. In addition, spontaneous suckling events elicit a release of cortisol.     

Plasma estrone sulphate (E1S) and estradiol-17beta (E2beta) profiles during pregnancy and their relationship with the relaxation of sacrosciatic ligament, and prediction of calving time in Holstein-Friesian cattle

The objectives of this study were to investigate the plasma E(1)S and E(2)beta profiles during pregnancy and their relationship with the relaxation of sacrosciatic ligament in Holstein-Friesian cattle (n=37) and then to predict the calving time on the basis of E(1)S and E(2)beta profiles and relaxation of the ligament. Blood samples were collected at 4 weeks intervals from days 100 to 190, at 2 weeks intervals from days 190 to 250, every week from days 250 to 270 and thereafter every day from day 270 of gestation until the day after calving. The relaxation in the ligament was measured by using two scales as a distance at a schedule similar to blood sampling plus 5 days postpartum. One scale was kept firm exactly parallel to the ligament between the sacrum and the tuber ischii and other scale was erected perpendicularly to the first scale with the bottom just touching the ligament and the depth was measured in the second scale from the point where it touched the ligament to the point where it touched the first scale. Plasma samples were analyzed for E(1)S and E(2)beta by enzyme immunoassay. E(1)S concentration was low at day 100 (0.8+/-0.3 ng/ml), then increased progressively and drastically to reach the level of 28.4+/-3.6 ng/ml on the day before calving and declined significantly (p<0.05) at 9.5+/-3.1 ng/ml within 1 day postpartum. There was a gradual increase in concentration of E(2)beta from day 100 of gestation (0.1+/-0 ng/ml) until day 4 prepartum (0.6+/-0 ng/ml). Thereafter, it increased drastically and reached the peak level of 1.0+/-0.1 ng/ml (p<0.05) on the day before calving and declined markedly at 0.4+/-0.1 ng/ml within 1 day postpartum (p<0.05). Corresponding to E(1)S and E(2)beta concentrations, a gradual increase in the relaxation of the ligament was observed from day 100 of gestation (8+/-1mm) until day 2 prepartum (24+/-2mm). Thereafter, it showed a significant increase (p<0.05) within 1 day before calving (31+/-2mm) and almost no difference between day 1 prepartum and day 1 postpartum. A marked decrease (p<0.05) was observed thereafter until day 3 postpartum (10+/-2mm) and no significant change between days 3 and 4 as well as 4 and 5 postpartum. The increment of E(2)beta by >or=0.20 ng/ml from the preceding day concentration was 85.2% accurate for predicting calving within 24h in many of the cows (23 of 37) in the herd. The increment in ligament relaxation measurement by >or=5mm from the preceding day measurement was the most efficacious to predict calving within 24h with the highest accuracy (93.9%) in high proportions of cows (31 of 37) in the herd. In conclusion, plasma E(1)S and E(2)beta concentrations and relaxation of sacrosciatic ligament increased gradually as gestation advanced and reached the peak level on the day before calving. The relaxation in the ligament corresponded well to plasma E(2)beta concentrations. Prediction of calving was possible by E(2)beta profile and relaxation in the ligament but not by E(1)S profile. The increment in ligament measurement by >or=5mm from the preceding day measurement was the most useful and accurate in predicting calving within 24h. It is economical and easily applicable in the field condition.     

Variables associated with peripartum traits in dairy cows. V. Hormonal profiles associated with retained fetal membranes

Profiles of certain hormones measured by radioimmunoassay in 41 Holstein cows and heifers with retained fetal membranes (RFM; >12 hr postpartum) were compared to 41 peers without RFM (NRFM). Peers were matched by parity, season of calving, gestation length, dystocia and parturient paresis within prepartum diet group. Linear covariates of natural photoperiod, mean daily temperature, calf birth weight, length of gestation, and age and body weight of cow were included in the leastsquares analyses of data. Plasma profiles of prolactin and estrone were nearly identical from day 8 prepartum to day 2.5 postpartum. Plasma estradiol-17α was approximately one-third higher each day in group RFM (P<.05 across days) but estradiol-17β (Eβ) tended to be lower until day 2 prepartum (not significant). Also, plasma progesterone (P) was higher in group RFM between days 8 to 3 prepartum (p<.05 across days).Relationships between plasma P and Eβ were indicative of subsequent RFM (>24 hr rather than >12 hr), but only on day 6 prepartum. Three of four cases of 12 to 24 hr RFM had P and Eß profiles similar to NRFM. Either a combination of low P (<3.0 ng/ml) and low Eß (<100 pg/ml) or only high P (>7.9 ng/ml) were associated with a ten-fold higher rate of RFM (>24 hr) than when P was intermediate (4 to 8 ng/ml) and Eß exceeded 99 pg/ml. These results are in agreement with prior data wherein RFM were induced at premature births either by ovariectomy during pregnancy or by glucocorticoids.     

The determination of the vitamin D metabolites on a single plasma sample: changes during parturition in dairy cows.

Methods have been developed for the precise measurement of the major known vitamin D metabolites in a single sample of cow plasma (~5 ml). The procedure involves initial extraction with methylene chloride-methanol followed by chromatography on Sephadex LH-20. 25-Hydroxyvitamin D₂ and 25-hydroxyvitamin D₃ were determined using high-pressure liquid chromatography and comparing ultraviolet absorption peak height with absorption peak heights of standards. The dihydroxylated metabolites were further purified and resolved by high-pressure liquid chromatography and determined by radioligand binding assays. The assays were employed to measure the total vitamin D metabolite levels in the plasma of paretic and normal dairy cows at parturition. Parturition had no effect on 25-hydroxyvitamin D levels in either group of cows (paretic, 37–44 ng/ml; normal, 35–38 ng/ml). However, normal cows did show lower mean 25-hydroxyvitamin D levels at every sampling period with the lowest levels in both groups occurring at 7 days postpartum. Plasma 25, 26-dihydroxyvitamin D was higher in paretic animals prepartum and at parturition (0.7–1.0 ng/ml) when compared to nonparetic animals (0.4–0.45 ng/ml). Similar levels (0.6 ng/ml) were observed in both groups postpartum. Cows developing parturient paresis showed a significant (P < 0.05) elevation of 1,25-dihydroxyvitamin D at parturition with a maximum level of 350 pg/ml attained at 1 day postpartum compared to prepartum levels of 60 pg/ml. Normal animals also showed a rise in plasma levels of 1,25-dihydroxyvitamin D with a maximum level of 185 pg/ml observed at 1 day postpartum. Plasma 24,25-dihydroxyvitamin D was initially higher in paretic cows (1.9 ng/ml) with a significant (P < 0.05) drop to 1.05 ng/ml occurring at parturition. This level was maintained for 7 days postpartum. The levels of this steroid were maintained at 1.3–1.4 ng/ml in the normal cows throughout the entire sampling period.     

Effect of nutrition on the LH response to calf removal and GnRH

Ten primiparous crossbred cows were assigned to two dietary groups at calving. One group received 120% and the other group received 80% of the National Research Council (NRC) recommended allowance of dietary energy for primiparous cows. At 60 days postpartum, calves were removed from their dams. Blood samples were collected from the cows at 15-min intervals for 8 hr beginning at the time of calf removal and again 24 hr, 48 hr and 72 hr after calf removal. At 72 hr after calf removal, all cows were given 200 ug GnRH intravenously. At calf removal, serum LH concentrations were higher (P<0.01) for cows on 120% (0.9 +/- 0.03 ng/ml) compared to cows on 80% (0.5 +/- 0.03 ng/ml) of recommendations. Serum LH concentrations increased (1.6 +/- 0.1 ng/ml, P<0.01) by 24 hr in cows on the highenergy diet. In contrast, a similar increase was not observed in cows on the low-energy diet until 48 hr after calf removal (1.4 +/- 0.2 ng/ml, P<0.01). These contrasting patterns in serum LH concentrations resulted in a diet by time interaction (P<0.01). Serum LH concentrations increased in both dietary energy groups following GnRH injection, but the response was greater (P<0.01) in cows on the low-energy diet compared to the cows fed the high-energy diet. These results indicate that inadequate dietary energy delays the LH response to calf removal and increases the LH response to exogenous GnRH.     

The importance of prolactin for initiation of lactation in the pregnant ewe

A single injection of ergocryptine (0.5 mg/kg liveweight) given to ewes 0.5-20 days prepartum or two injections (0.5 mg/kg liveweight per injection) given c. 30 and 10 days prepartum reduced concentrations of plasma prolactin to negligible (less than 5 ng/ml) values for 4 weeks after parturition, but did not affect concentrations of growth hormone and placental lactogen. Milking of treated ewes had no effect on concentrations of plasma prolactin during the first 4 weeks of lactation, but concentrations of growth hormone were increased during the 10-20 min period after milking. The half-life of prolactin in plasma was estimated as 21 min. In spite of the dramatic effect of ergocryptine on plasma prolactin all treated ewes secreted copious quantities of milk of normal composition. Mean daily yields of ewes treated with ergocryptine were not significantly different (P greater than 0.05) from those of untreated control ewes, but the mean +/- s.e.m. of total milk production over the first 3 weeks of lactation for ergocryptine-treated ewes was significantly lower (P less than 0.05) than that of control ewes (9.5 +/- 1.11 v. 14.1 +/- 1.20 kg milk). The results suggest that prolactin is not an essential component of the lactogenic and galactopoietic complexes of hormones in the ewe.     

Effect of suckling on cortisol, progesterone and luteinizing hormone in postpartum beef cows

Five primiparous, 3-year-old Hereford cows suckled ad libitum , were cannulated via the jugular vein and stanchioned for 2-day sampling periods, every 14 days starting 14 days after the mean calving date. On the second day of each period, calves were removed to a pen away from the cows, for 9 hours. Blood was sampled 5 min before calves were returned to their dams, as soon as possible after initiation of suckling (IOS), and at 15-min intervals for 45 min, thereafter. Cortisol, progesterone and luteinizing hormone (LH) concentrations in the serum were quantitated by radioimmunoassay. Mean serum cortisol concentrations were 7.3 +/- .7, 9.4 +/- .7, 12.1 +/- .9, 7.5 +/- .5 and 5.7 +/- .4 ng/ml (mean +/- S.E.) at -5, 0, 15, 30 and 45 min after IOS, respectively, for all cows across all periods. Cortisol concentrations, during and after suckling, tended (P<.06) to differ among sampling periods, during the postpartum interval. Serum progesterone concentrations were .28 +/- .02, .28 +/- .02, .32 +/- .05 and .24 +/- .03 ng/ml at 0, 15, 30 and 45 min after IOS, respectively, for all cows across all period, indicating that suckling had no effect on serum progesterone, and were similar at all sampling periods during the postpartum interval. Serum LH concentrations were .81 +/- .07, .77 +/- .06, .71 +/- .04, and .72 +/- .04 ng/ml at 0, 15, 30 and 45 min after IOS, respectively. During the postpartum interval, serum LH concentrations were greater (P<.01) at 71 and 85 days postpartum than at any other time.     

Inhibition of dipeptidyl-peptidase IV does not increase circulating IGF-1 concentrations in growing pigs

The enzyme dipeptidyl peptidase-IV (DPP-IV) inactivates a variety of bioactive peptides, including glucagon-like peptide-1 (GLP-1) and growth hormone releasing hormone (GHRH). Inhibiting DPP-IV in order to increase circulating GLP-1 is of interest as a treatment for Type II diabetes. Inactivation of DPP-IV may also increase circulating GHRH, potentially enhancing growth in domestic animals. To test the hypothesis that inhibition of DPP-IV activity will influence the growth hormone/ IGF-1 axis, growing pigs (Sus scrofa domesticus, 78 kg) were treated with a DPP-IV inhibitor (Compound 1, the 2,5-difluor-ophenyl analog of the triazolopiperazine MK0431, sitagliptin), and plasma concentrations of IGF-1 were monitored. Pigs were administered either sterile saline (0.11 ml/kg followed by a continuous infusion at 2 ml/hr for 72 hrs, controls, n = 2), Compound 1 (2.78 mg/kg followed by a continuous infusion at 0.327 mg/kg x hr for 72 hrs, n = 4) or GHRH (0.11 ml/kg sterile saline, followed by a continuous infusion of GHRH at 2.5 microg/ kg x hr for 48 hrs, n = 4). Plasma concentrations of Compound 1 were maintained at 1 microM, which resulted in a 90% inhibition of circulating DPP-IV activity. Relative to the predose 24-hr period, area under the IGF-1 concentration curve (AUC) tended to be lower (P = 0.062) with Compound 1 (.79 +/- 130 ng/ml x hr) than controls (543 +/- 330 ng/ml x hr). GHRH treatment increased the IGF-1 AUC (1210 +/- 160 ng/ml x hr, P = 0.049 vs. controls and P = 0.001 vs. Compound 1). We conclude that inhibition of DPP-IV does not alter the circulating levels of IGF-1 in the growing pig.     

Pregnancy alters cortisol feedback inhibition of stimulated ACTH: studies in adrenalectomized ewes

These studies test the hypothesis that pregnancy alters the feedback effects of cortisol on stimulated ACTH secretion. Ewes were sham-operated (Sham), or adrenalectomized (ADX) at approximately 108 days gestation and replaced with aldosterone (3 microg x kg(-1) x day(-1)) and with cortisol at either of two doses (ADX + 0.6 and ADX + 1 mg x kg(-1) x day(-1)); ewes were studied during pregnancy and postpartum. Mean cortisol levels produced in ADX ewes were similar to normal pregnant ewes (ADX+1) or nonpregnant ewes (ADX+0.6), respectively. Plasma ACTH concentrations in response to infusion of nitroprusside were significantly increased in the pregnant ADX+0.6 ewes (1,159 +/- 258 pg/ml) relative to pregnant Sham ewes (461 +/- 117 pg/ml) or the ADX+1 ewes (442 +/- 215 pg/ml) or the same ewes postpartum (151 +/- 69 pg/ml). Plasma ACTH concentrations were not significantly different among the groups postpartum. Increasing plasma cortisol to 20-30 ng/ml for 24 h before hypotension produced similar inhibition of ACTH in all groups. Pregnancy appears to decrease the effectiveness of low concentrations of cortisol to inhibit ACTH responses to hypotension.     

Effects of leptin on fetal plasma adrenocorticotropic hormone and cortisol concentrations and the timing of parturition in the sheep

We investigated whether leptin can suppress the prepartum activation of the fetal hypothalamus-pituitary-adrenal (HPA) axis and delay the timing of parturition in the sheep. First, we investigated the effects of a 4-day intravascular infusion of recombinant ovine leptin (n = 7) or saline (n = 6) on fetal plasma adrenocorticotropic hormone (ACTH) and cortisol concentrations, starting from 136 days gestation (i.e., at the onset of the prepartum activation of the fetal HPA axis. The effects of a continuous intrafetal infusion of leptin (n = 7) or saline (n = 5) from 144 days gestation on fetal plasma ACTH and cortisol concentrations and the timing of delivery were also determined in a separate study. There was an increase in fetal plasma ACTH (P < 0.01) and cortisol (P < 0.001) concentrations when saline was infused between 136-137 and 140-141 days gestation. Plasma ACTH and cortisol concentrations did not rise, however, when leptin was infused during this period of gestation. When leptin was infused after 144 days gestation, there was no effect of a 4- to 5-fold increase in circulating leptin on fetal ACTH concentrations. In contrast, leptin infusion from 144 days gestation suppressed (P < 0.05) fetal plasma cortisol concentrations by around 40% between 90 and 42 h before delivery. There was no difference, however, in the length of gestation between the saline- and leptin-infused groups (saline infused, 150.2 +/- 0.5 days; leptin infused, 149.8 +/- 1.0 days). In saline-infused fetuses, there was a significant negative relationship between the plasma concentrations of cortisol (y) and leptin (x) between 138 and 146 days gestation (y = 81.4 - 7.7x, r = 0.38, P < 0.005). This study provides evidence for an endocrine negative feedback loop between leptin and the HPA axis in fetal life.     

Plasma prolactin in the periparturient sow

A homologous radioimmunoassay was used for measurement of porcine prolactin in blood plasma collected from sows during the periparturient period. The assay was able to detect prolactin over a range of 0.5 to 7.0 ng/assay tube. There was no significant cross reaction with growth hormone, luteinizing hormone, or follicle stimulating hormone at amounts up to 10⁵ ng/assay tube while porcine ACTH gave 30% binding at 10⁴ ng. Prolactin was not detected in plamsa from a hypophysectomized pig or 2 ergocryptine-treated sows when 100 μ l plasma were assayed. Prolactin concentration in plasma was then measured in 14 periparturient sows within a period extending from 7 days before farrowing to 7 days after farrowing. Samples were collected at 15 min intervals between 1330 and 1630 h each day. However, prolactin assays were done only on the even-numbered samples (30 min interval). Plasma prolactin concentrations (ng/ml, $\text{X}\text{± SEM}$) were 23.7 ± 2.0 on days ?7 to ?5 prepartum, began to rise by day ?3 prepartum (42.5 ± 5.9), and peaked at 127.5 ± 17.6 on day 1 prepartum. By day 3 postpartum, prolactin concentrations in plasma had decreased to 80.5 ± 12.6 and further declined to 51.6 ± 4.6 on day 7 postpartum. The mean prolactin concentration in plasma for all pigs on days ?1 to +2 was 116.8 ± 13.8. This mean concentration for days ?1 to +2 was different (P < 0.025) from the mean prolactin concentration for the period both prior and subsequent to these days (?8 to ?2 and +3 to +8 days).     

Relationship between LH and cortisol in acutely stressed beef cows

The influence of handling stress on tonic LH secretion was evaluated in eight ovariectomized Hereford cows. Four cows (acclimated group) were previously acclimated to stanchions and procedures for blood collection, whereas the other four cows (unacclimated group) were stanchioned and handled for the first time 2 hr before the evaluation period. Blood samples (10 ml) for cortisol, luteinizing hormone (LH) and progesterone quantitation were collected at 10-min intervals for 4 hr via an indwelling cannula inserted into the jugular vein 1 hr before the evaluation period. Mean plasma concentration of cortisol was lower (5.7 vs 66.1 ng/ml; P<0.01) but LH was higher (8.1 vs 4.1 ng/ml; P<0.05) in acclimated cows than in unacclimated cows. Plasma cortisol and LH concentrations were correlated negatively among cows (r = -0.83; P<0.01). Two- to four-fold increases (10 to 20 ng/ml) in systemic cortisol concentrations did not appear to affect LH secretion, whereas 10-to 20-fold increases associated with intensive stress suppressed tonic LH secretion, especially pulsatile LH releases. Plasma progesterone concentrations did not differ between the two treatment groups. Results suggest that the influence of stress on gonadotropin secretion, and subsequent reproductive responses, is dependent on the magnitude of the adrenal steroidogenic response and the animal's adaptation to stress. These results indicate the necessity to minimize and monitor animal stress when studying LH secretion.     

ACTH does not mediate divergent stress responsiveness in rainbow trout.

Two lines of rainbow trout selected for high (HR) and low (LR) responsiveness to a standardised confinement stressor displayed a sustained divergence in plasma cortisol levels during a 3-h period of confinement (max.: HR: 167+/-13 ng ml(-1); LR: 103+/-8 ng ml(-1); P<0.001). However, no significant difference in plasma ACTH levels was evident (max: HR: 153+/-9 pg ml(-1); LR: 142+/-7 pg ml(-1)). Dexamethasone (DEX) was administered to HR and LR fish to block endogenous adrenocorticotropin (ACTH) release. Administration of a weight-adjusted dose of ACTH to the DEX-blocked fish elevated plasma cortisol levels to a significantly greater extent in HR (233+/-24 ng ml(-1)) than LR (122+/-14 ng ml(-1)) fish (P<0.001). Plasma cortisol levels in DEX-blocked HR and LR fish after sham injection were low but also significantly different (HR: 6.7+/-1 ng ml(-1); LR: 2.2+/-0.2 ng ml(-1); P<0.001). These results indicate that modulation of cortisol responsiveness to stressors in HR and LR fish resides, at least in part, downstream of the hypothalamic-pituitary axis.     

Seasonal variations in plasma hormones and reproductive efficiency in early postpartum buffalo

Investigations were carried out on twenty newly calved Murrah buffalo that were divided into two sets of ten each during winter (December to February) and summer (May to September). Recommended feeding and management practices were followed. Blood samples were collected on Days 0, 1, 2, 4, 6, 8, 15, 22, 29, 36, 43, 50 and 57 postpartum for hormone radioimmune assay (RIA). The values of reproductive parameters and hormone levels during winter and summer, respectively, were the following for uterine involution, 39.50 +/- 2.74 d and 32.50 +/- 3.01 d; first postpartum estrus interval, 70.10 +/- 9.62 d and 37.40 +/- 11.82 d; number of services per conception, 1.57 +/- 0.29 and 2.40 +/- 0.68; first service conception rate, 40 and 20 %, overall conception rate, 70 and 40 %; 13,14-Dihydro-15-keto prostaglandin F(2alpha) (PGFM), 1.78 +/- 0.26 ng/ml and 2.62 +/- 0.30 ng/ml; progesterone, 1.09 +/- 0.14 ng/ml and 0.65 +/- 0.77 ng/ml. A negative correlation (r = -0.83, P 0.05 ) was observed between PGFM and progesterone. Although, summer stress hastens uterine involution and first postpartum estrus interval, overall reproductive efficiency is impaired due to deficiency of progesterone, which is essential for embryo survival.     

Stimulation of the pituitary adrenocortical system in man by cerulein, a cholecystokinin-8-like peptide

The responses of plasma adrenocorticotropin hormone (ACTH) and cortisol to intravenous injection of cerulein (ceruletide), a decapeptide closely related to cholecystokinin octapeptide, were investigated in healthy men. In response to 16 ng/kg cerulein, plasma ACTH rose from a preinjection level of 42 +/- 11 pg/ml (mean +/- SEM) to a peak level of 81 +/- 16 pg/ml after 15 min. This ACTH increase was followed by a rise in plasma cortisol from a preinjection value of 10.3 +/- 0.9 microgram/dl to a peak value of 17.7 +/- 1.7 microgram/dl after 30 min. This is the first report of the potent stimulating effect of a cholecystokinin-8-related peptide on the pituitary-adrenal system in man.     

Effect of prepartum somatotropin injection in late-pregnant Holstein heifers on metabolism, milk production and postpartum resumption of ovulation

The aim of this study was to determine the effect of prepartum somatotropin injection in late-pregnant Holstein heifers on metabolism, milk production and resumption of postpartum ovulation. For this study, 31 late-pregnant Holstein heifers were used. The heifers were assigned randomly into two treatments: (1) 500 mg sc injections of somatotropin (somatotropin treatment, n = 15) at -35 and -21 days, and, if pertinent, at -7 days from expected calving date and (2) no treatment (control group, n = 16). Blood samples were collected weekly from -5 to 7 weeks after calving. Heifers with progesterone concentrations in plasma above 1 ng/ml in two consecutive postpartum samples were considered as having resumed ovarian activity. A higher proportion (P = 0.04) of heifers treated with somatotropin resumed ovarian activity in the first 7 weeks post partum (73.3%; 11/15) compared with the control group (37.5%; 6/16). A higher number (P = 0.02) of heifers in the somatotropin treatment group also ovulated during the first postpartum follicular wave (53.3%; 8/15) compared with the control group (12.5%; 2/16), as indicated by the number of heifers ovulating in the first 3 weeks post partum. Pregnancy rate was not affected by treatments (P > 0.10) and averaged 40.0% (6/15) in somatotropin-treated and 25.0% (4/16) in control heifers when evaluated up to 150 days in milk. Somatotropin treatment increased the average daily milk production by 2.8 kg/cow per day (P < 0.0001) and reduced the somatic cell count (P = 0.009). Plasma IGF-I was higher (P < 0.05) for somatotropin-treated heifers in the prepartum period. Insulin and body condition score were higher (P < 0.05) and non-esterified fatty acids were lower (P < 0.05) for somatotropin-treated cows in the early postpartum period. In conclusion, somatotropin injection during the prepartum period in late-pregnant Holstein heifers was able to increase the proportion of heifers resuming ovarian activity early post partum, inspite of higher milk production.     

Pharmacokinetic and pharmacodynamic interactions between simvastatin and diltiazem in patients with hypercholesterolemia and hypertension

Pharmacokinetic and pharmacodynamic interactions between simvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, and diltiazem, a calcium antagonist, were investigated in 7 male and 4 female patients with hypercholesterolemia and hypertension. The patients were given, for one in a three consecutive 4-week periods, oral simvastatin (5 mg/day), oral simvastatin (5 mg/day) combined with diltiazem (90 mg/day), and then oral diltiazem (90 mg/day), respectively. The area under the plasma concentration versus time curve up to 6 hours post-dose (AUC0-6h) and maximum plasma concentrations (Cmax) of the drugs, serum lipid profiles, blood pressures and liver functions were assessed on the last day of each of the three 4-week periods. After the combined treatment period, Cmax of HMG-CoA reductase inhibitor was elevated from 7.8 +/- 2.6 ng/ml to 15.4 +/- 7.9 ng/ml (P < 0.01) and AUC0-6h from 21.7 +/- 4.9 ng x hr/ml to 43.3 +/- 23.4 ng x hr/ml (P < 0.01), while Cmax of diltiazem was decreased from 74.2 +/- 36.4 ng/ml to 58.6 +/- 18.9 ng/ml (P < 0.05) and its AUC0-6h from 365 +/- 153 ng x hr/ml to 287 +/- 113 ng x hr/ml (P < 0.01). Compared to simvastatin monotherapy, combined treatment further reduced LDL-cholesterol levels by 9%, from 129 +/- 16 mg/dl to 119 +/- 17 mg/dl (P < 0.05). No adverse events were observed throughout the study. These apparent pharmacokinetic interactions, namely the increase of HMG-CoA reductase inhibitor concentration by diltiazem and the decrease of diltiazem concentration by simvastatin, enhance the cholesterol-lowering effects of simvastatin during combined treatment.