Comparison of 2 Doses for ACTH Stimulation Testing in Dogs Suspected of or Treated for Hyperadrenocorticism.

BACKGROUND: Lowering the cosyntropin dose needed for ACTH stimulation would make the test more economical. OBJECTIVES: To compare the cortisol response to 1 and 5 µg/kg cosyntropin IV in dogs being screened for hyperadrenocorticism (HAC) and in dogs receiving trilostane or mitotane for pituitary-dependent HAC. ANIMALS: Healthy dogs (n = 10); client-owned dogs suspected of having HAC (n = 39) or being treated for pituitary-dependent HAC with mitotane (n = 12) or trilostane (n = 15). PROCEDURES: In this prospective study, healthy dogs had consecutive ACTH stimulation tests to ensure 2 tests could be performed in sequence. For the first test, cosyntropin (1 µg/kg IV) was administered; the second test was initiated 4 hours after the start of the first (5 µg/kg cosyntropin IV). Dogs suspected of having HAC or being treated with mitotane were tested as the healthy dogs. Dogs receiving trilostane treatment were tested on consecutive days at the same time post pill using the low dose on day 1. RESULTS: In dogs being treated with mitotane or trilostane, the 2 doses were pharmacodynamically equivalent (90% confidence interval, 85.1-108.2%; P = 0.014). However, in dogs suspected of having HAC, the doses were not pharmacodynamically equivalent (90% confidence interval, 73.2-92.8%; P = 0.37); furthermore, in 23% of the dogs, clinical interpretation of test results was different between the doses. CONCLUSIONS AND CLINICAL RELEVANCE: For dogs suspected of having HAC, 5 µg/kg cosyntropin IV is still recommended for ACTH stimulation testing. For dogs receiving mitotane or trilostane treatment, a dose of 1 µg/kg cosyntropin IV can be used.

Animal models of Cushing's disease.

Cushing's disease, defined as hyperadrenocorticism resulting from excessive secretion of pituitary ACTH, occurs spontaneously and quite commonly in dogs and horses. In dogs, as in humans, the disease is usually associated with a small tumor of the pituitary pars distalis. However, the disease may arise occasionally (dogs) or exclusively (horses) from tumors or hyperplasia of the pituitary pars intermedia. In dogs, pars intermedia tumors may arise from one of two proopiomelanocortin-containing cell types that are present in normal tissue.

Characterization of the hydroxycarboxylic acid receptor 2 in cats.

The hydroxycarboxylic acid receptor 2 (HCA2) belongs to a family of nutrient-sensing receptors that bind ß-hydroxybutyrate, an alternative fuel source produced during a negative energy balance. The HCA2 receptor has not been identified or characterized in cats. Therefore, the following were the objectives of this study: (1) identify the feline HCA2 receptor protein sequence and compare against known human and rodent sequences, (2) determine tissue distribution and relative expression in lean, healthy cats, and (3) demonstrate in vitro functionality in feline adipose tissue. Tissues (n = 6) and primary adipocytes (n = 4) were collected from lean, healthy, female cats. The published genomic sequence for cats was used to design primers for polymerase chain reaction isolation of HCA2. Relative tissue distribution was evaluated using reverse transcriptase-polymerase chain reaction with RNA isolated from 9 different tissues (spleen, pancreas, lymph node, jejunum, kidney, liver, heart, and subcutaneous and abdominal adipose tissue). Receptor function was evaluated in primary feline adipocyte culture, and changes were compared with basal lipolysis. The in silico predicted feline HCA2 protein sequence exhibited 83.1% and 86.5% amino acid similarity to human and mouse sequences, respectively. The feline HCA2 receptor is predominantly expressed in adipose tissue and spleen. Exposure of feline adipocytes to niacin, a pharmacologic ligand of HCA2, inhibited lipolysis to a similar degree as insulin, a potent lipolytic inhibitor. In conclusion, the feline HCA2 receptor is similar to human and murine receptors in sequence, distribution, and functionality. By gaining a better understanding of the HCA2 receptor in cats, we will be able to better manage feline patients.

Evaluation of thyroid-stimulating hormone, total thyroxine, and free thyroxine concentrations in hyperthyroid cats receiving methimazole treatment.

BACKGROUND: Iatrogenic hypothyroidism (IH) after treatment of hyperthyroidism can impair renal function. No study compared the efficacy of measurement of serum free thyroxine by equilibrium dialysis (fT4ed) or thyroid-stimulating hormone (TSH) concentrations for monitoring cats receiving methimazole. OBJECTIVES: To (1) compare the ability of total T4 and fT4ed concentrations in conjunction with TSH to define thyroid function in hyperthyroid cats receiving methimazole, (2) determine the prevalence of IH in cats receiving methimazole, and (3) examine the relationship between thyroid axis hormones and serum creatinine concentration. ANIMALS: One hundred and twenty-five serum samples from hyperthyroid cats receiving methimazole and total T4 concentrations ≤3.9 µg/dL. METHODS: Total T4, fT4ed, and TSH concentrations were measured to evaluate thyroid status and serum creatinine concentration was measured to assess renal function. A low total T4 or fT4ed concentration in combination with an increased TSH concentration defined IH. RESULTS: Forty-one cats (33%) had increased TSH concentrations. Of cats with total T4 and fT4ed concentrations below the reference range, 68% and 73%, respectively, had TSH concentrations above the reference range. Only 18% of cats with a normal TSH concentration had an increased serum creatinine concentrations as compared to 39% of those with increased TSH concentrations (P < .001). CONCLUSIONS: Free T4ed does not identify more cats with potential IH as compared to total T4. The IH prevalence was approximately 20%. Measurement of TSH may be more helpful in indicating that azotemia, if present, is at least in part related to IH. Investigation is needed to define TSH assay utility in identifying possible subclinical IH.

Regulation and secretion of proopiomelanocortin peptides from isolated perifused dog pituitary pars intermedia cells.

The dog pituitary pars intermedia (PI) appears to consist of relative large numbers of ACTH-containing cells in addition to the more abundant alpha MSH-containing cells. Since regulation of PI secretion probably varies across mammalian species, this study was undertaken to identify substances potentially involved in the control of dog PI POMC peptide secretion and to determine if these substances altered the secretion of immunoreactive (IR) ACTH and IR-alpha MSH in a parallel fashion. Pituitary neurointermediate lobes from dogs were collected and dispersed, and the PI cells obtained were perifused. For comparison, rat PI and pars distalis (PD) cells as well as dog PD cells were similarly collected and perifused. Dog PI cells secreted IR-alpha MSH at a basal rate of 125 +/- 59 (mean +/- SD) pg/min.10(5) cells and IR-ACTH at a rate of 40 +/- 9 pg/min.10(5) cells (molar IR-alpha MSH/IR-ACTH = 10). In contrast, secretion rates for IR-alpha MSH and IR-ACTH from perifused rat PI cells were 171 +/- 108 and 3 +/- 2 pg/min.10(5) cells, respectively (molar IR-alpha MSH/IR-ACTH = 179). Using Sephadex G-50 gel filtration chromatography, virtually all of the IR-beta-endorphin secreted by dog PI cells eluted near beta-endorphin (1-31). In addition, all of the IR-alpha MSH secreted by dog PI cells coeluted with synthetic alpha MSH on the G-50 column, but IR-ACTH appeared in two peaks, one eluting near porcine ACTH-(1-39) and another, apparently larger mol wt species. Dopamine and somatostatin were found to inhibit the secretion of IR-alpha MSH and IR-ACTH from perifused dog PI cells in a parallel and dose-dependent fashion. Norepinephrine and epinephrine similarly inhibited POMC peptide secretion, but this effect was blocked by haloperidol, suggesting that it was mediated through a dopamine receptor. CRF stimulated the secretion of both hormones from dog PI, and this effect was abolished by treatment of the cells with either dopamine or somatostatin. Cortisol had no effect on either basal or CRF-stimulated secretion of IR-alpha MSH or IR-ACTH from dog PI cells, but it did inhibit CRF-stimulated IR-ACTH from perifused dog PD. These results suggest that 1) dog PI secretes considerably more IR-ACTH than that in the rat; 2) the probable separate cell sources of IR-alpha MSH and IR-ACTH in dog PI are regulated in an identical fashion; and 3) dopamine, somatostatin, and CRF may function in the physiological or pathophysiological regulation of dog PI.

Differential secretion of pro-opiomelanocortin peptides by the pars distalis and pars intermedia of beagle dogs.

Beagle dogs were given saline, insulin or the dopamine antagonist, haloperidol, to examine peripheral concentrations of immunoreactive (ir)-pro-opiomelanocortin (POMC) peptides resulting from pars distalis or pars intermedia stimulation. Six beagles were given each test substance on separate occasions with and without dexamethasone pretreatment. Plasma was assayed directly for glucose, ir-ACTH, ir-alpha-MSH, cortisol and, after Sephadex G-50 Fine gel filtration chromatography, for ir-beta-lipotrophin (ir-beta-LPH) and ir-beta-endorphin (ir-beta-END) content. Injection of 0.5 units insulin/kg lowered (P less than 0.01) plasma glucose from 4.9 +/- 0.3 mmol/l (mean +/- S.D., saline controls) to 2.3 +/- 0.5 mmol/l, coincident with increasing ir-ACTH (9.5 +/- 3.1 to 106 +/- 54 pmol/l), cortisol (52 +/- 27 to 221 +/- 27 nmol/l), ir-beta-LPH (not detectable to 34 +/- 18 pmol/l) and ir-beta-END (not detectable to 52 +/- 22 pmol/l). Plasma ir-alpha-MSH concentrations were not affected by insulin. Pretreatment with dexamethasone abolished the ir-ACTH, cortisol, ir-beta-LPH and ir-beta-END increases in response to 0.75 units insulin/kg. Haloperidol (1 mg/kg) increased (P less than 0.01) plasma ir-ACTH (to 103 +/- 63 pmol/l), cortisol (to 243 +/- 11 nmol/l), ir-beta-LPH (to 16 +/- 6 pmol/l), ir-beta-END (to 136 +/- 73 pmol/l) and additionally raised ir-alpha-MSH (7 +/- 8 pmol/l in saline controls to 131 +/- 80 pmol/l after haloperidol).(ABSTRACT TRUNCATED AT 250 WORDS)

Evidence for episodic but not circadian activity in plasma concentrations of adrenocorticotrophin, cortisol and thyroxine in dogs.

Concentrations of immunoreactive (i) ACTH, cortisol and thyroxine were determined in plasma samples obtained at 20-min intervals for 25 h in nine normal and two adrenalectomized dogs. The dogs were exposed to a 12 h light: 12 h darkness photoperiod for 30 days before the sampling period. Episodic secretion of iACTH and cortisol was evident in each normal dog, with an average of 9.0 iACTH peaks and 10.1 cortisol peaks in a 24-h period. Levels of iACTH and cortisol were significantly correlated in each normal dog, but periods of dissociation between levels of the two hormones were apparent. A sex difference in 24-h mean iACTH and cortisol levels, numbers of cortisol peaks, and amplitude of iACTH peaks was observed, with females showing higher mean levels and greater peak frequency and amplitude in each instance. Adrenalectomy resulted in a 50- to 150-fold increase in mean iACTH concentrations with an apparent increase in iACTH peak amplitude. Cortisol levels were unchanging in the adrenalectomized dogs. Thyroxine concentrations showed episodic variation in each of the normal dogs, but the mean number of peaks (3.3/24-h period) was considerably less than for iACTH or cortisol. Female dogs a had significantly higher 24-h mean levels of thyroxine than did males. No circadian rhythmicity was obvious for the plasma levels of any of the three hormones measured.

Cortisol inhibition of growth hormone-releasing hormone-stimulated growth hormone release from cultured sheep pituitary cells.

Cortisol inhibits growth hormone (GH) release in short-term culture and is stimulatory in long-term cultures of rat and human pituitary cells. This study sought to determine the in vitro effects of cortisol on GH release and the signal transduction pathways mediating the effects of cortisol on GH release from cultured ovine somatotrophs. Pituitary cells were dispersed with collagenase and placed in culture medium for 4 days. The data indicate that cortisol inhibited growth hormone-releasing hormone (GHRH)-stimulated GH release by at least 2 h. In short-term culture GHRH-, forskolin- and dibutyryl cyclic AMP-stimulated GH release were inhibited by cortisol, suggesting an effect distal to the membrane and involving a protein kinase A (PKA)-dependent pathway. GH release initiated by KCl was inhibited by cortisol, but GH release caused by the calcium ionophore A23187 was unaffected. This suggests a possible action of cortisol on the calcium channels. The inhibition by cortisol of the calcium-dependent secretion of GH release appeared to play a smaller role in mediating cortisol inhibition of GH release than that seen with PKA. Attempts to overcome cortisol inhibition of GH release using puromycin, arachidonic acid or pertussis toxin were unsuccessful. Since cortisol inhibition of GH release does not occur via the mechanisms found in other cell types, cortisol inhibition of pituitary cell secretions appears to be cell-specific rather than utilizing a single inhibitory mechanism. The majority of cortisol actions on the somatotroph appear to act at a site distal to the production of cyclic AMP.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of prednisone on thyroid and gonadal endocrine function in dogs.

To assess the effect of a glucocorticoid on thyroid and gonadal endocrine function, prednisone was administered on alternate days to dogs. The prednisone injections resulted in adrenocortical suppression, as shown by the response to ACTH. Basal plasma thyroxine and tri-iodothyronine concentrations were considerably reduced in prednisone-treated dogs. However, the thyroid response to injection of thyrotrophin-releasing hormone was not altered, indirectly demonstrating that pituitary release of TSH was not inhibited by prednisone. Similarly, the response of the thyroid to exogenous TSH was not reduced by prednisone treatment. Electron microscopic examination of thyroid tissue revealed accumulation of colloid droplets in the follicular cell cytoplasm of dogs treated with prednisone. It is postulated that prednisone may interfere with basal thyroid hormone secretion by inhibiting lysosomal hydrolysis of colloid in the thyroid follicular cell. Basal plasma concentrations of LH and testosterone, measured in the male dogs, were reduced by prednisone treatment. Responses of prednisone-treated dogs to luteinizing hormone releasing hormone were not significantly reduced. Prednisone administration did not alter testicular responsiveness to injection of human chorionic gonadotrophin. After orchidectomy, plasma LH values were significantly reduced in prednisone-treated dogs. Taken together, these results suggest that LH secretion in dogs is inhibited at the hypothalamic and/or pituitary level by prednisone administration, which consequently results in reduced testosterone concentrations.

Domestic cats show episodic variation in plasma concentrations of adrenocorticotropin, alpha-melanocyte-stimulating hormone (alpha-MSH), cortisol and thyroxine with circadian variation in plasma alpha-MSH concentrations.

Blood samples were collected from 31 healthy domestic cats to characterize possible episodic and/or circadian variation in plasma concentrations of adrenocorticotropin (ACTH), cortisol, thyroxine and alpha-melanocyte-stimulating hormone (alpha-MSH). Samples were collected with minimal disturbance through indwelling jugular cannulae at two frequencies: at 20-min intervals for 3 h for evaluation of episodic variation, and at 2-h intervals for 48 or 72 h to identify possible circadian changes. Episodic peaks in profiles of all hormones were found in the majority of cats. When data were compared across four bleed periods (each of 3 h duration), no differences were detected in average hormone concentrations or characteristics of episodic pulses. Correlation analyses showed a significant (p < 0.001) relationship between concentrations of ACTH and cortisol (r = 0.44) when these hormones were measured in the same plasma sample. A weaker but significant correlation (r = 0.13, p < 0.05) was also detected between concentrations of ACTH and alpha-MSH, suggesting that proopiomelanocortin peptide secretion from the pars distalis and pars intermedia occurs at least on occasion in synchrony. No differences in hormonal profiles were noted when comparing data across sexes. Data from the studies designed to evaluate circadian change (48 and 72-h bleed periods) indicated that, of the four hormones, only concentrations of alpha-MSH changed with a significant circadian periodicity. A significant circadian component of period length 24-25 h was detected in 37% (seven of 19) of cats examined. Concentrations of alpha-MSH were greatest coincident with or shortly after the onset of darkness. These findings indicate that pituitary-adrenocortical hormones are secreted episodically in domestic cats and that, in contrast to the patterns shown by ACTH and cortisol, secretion of the pars intermedia product alpha-MSH occurs with a circadian rhythm in about one-third of cats.

The relationship between autoantibodies to triiodothyronine (T3) and thyroglobulin (Tg) in the dog.

The relationship between T3 autoantibodies (T3AA) and thyroglobulin autoantibodies (TgAA) in dogs was investigated by determining the inhibitory effect of triiodothyronine (T3), thyroxine (T4) and thyroglobulin (Tg) on T3AA and TgAA binding activity and by determining the pattern of occurrence of the two activities in canine serum samples. Strong similarity in binding characteristics between the two activities, as one might expect if T3AA activity were merely a cross-reactivity of TgAA, was not observed. Canine T3AA activity exhibited a cross-reactivity to purified canine Tg that was intermediate between that of T3 and T4, indicating an antigenic relationship to an epitope of Tg. Average affinity constants of canine T3AA (N = 11) for T3, Tg and T4 were 1.76 x 10(10) M-1, 2.29 x 10(9) M-1, and 1.02 x 10(8) M-1, respectively. Canine TgAA activity, however, did not cross-react significantly with T3 or T4. Canine TgAA (N = 21) binding to canine Tg was not inhibited by T4 or T3 at concentrations up to 2 x 10(-4) M. Each of 23 canine serum samples containing T3AA also exhibited TgAA activity, although there was poor correlation between the magnitudes of the two activities. Neither T3AA nor TgAA activity was observed in serum samples from 16 euthyroid dogs; however, 46.7% of the samples from 15 hypothyroid dogs had detectable TgAA activity. T3AA is so rare that is was not observed in this small population of samples from hypothyroid dogs. The [125I] T3 binding in serum from hypothyroid dogs was elevated compared to that in euthyroid dogs, but was considerably lower than in samples generally designated as containing T3AA. These results suggest that T3AA found in occasional canine serum samples are due to the presence of autoantibodies recognizing a T3 containing epitope of Tg that is different from the epitopes involved in eliciting the predominant population of canine Tg autoantibodies.

Molecular forms of alpha-melanocyte-stimulating hormone in the canine pituitary anterior and intermediate lobe.

Reverse-phase high pressure liquid chromatography (HPLC) and radioimmunoassay (RIA) were used to determine the distribution of naturally occurring forms of alpha-melanocyte-stimulating hormone (alpha-MSH) in acid extracts of pars intermedia (PI) and anterior lobe (AL) tissue from canine and rat pituitary. Similarly, intracellular and secreted forms of alpha-MSH were determined using cultured canine PI and AL cells. Rat PI tissue contained predominantly diacetyl-alpha-MSH, while monoacetyl-alpha-MSH was the most abundant form in canine PI. In both canine and rat AL tissue extracts desacetyl-alpha-MSH was the major form of alpha-MSH. The profile of alpha-MSH contained in and secreted into culture medium by canine PI cells was found to be very similar to that in PI tissue extracts. The proportion of monoacetyl-alpha-MSH and diacetyl-alpha-MSH secreted by cultured canine AL cells and contained in extracts of AL cells in culture, however, was much higher than that in tissue extracts. These results indicate that in the dog, as in all other mammalian species studied, acetylated forms of alpha-MSH predominate in PI tissue, while nonacetylated alpha-MSH is the major form in AL tissue. It appears, however, that acetylation of alpha-MSH may occur in cultured canine AL cells, possibly as a result of the absence of factors that normally inhibit acetyltransferase in vivo or as a consequence of culture conditions.

Effects of steroids on the olfactory function of the dog.

Twenty-four (24) mature, mixed breed, healthy dogs weighing from 14.6 kg to 27.6 kg were used to study the effects of various steroids on the olfactory function of the dog using olfactory detection threshold as an index. Two odorants were used, viz; benzaldehyde and eugenol. Of the various steroids used, only dexamethasone produced classical signs of Cushing's syndrome in the dogs. However, all dogs that received either dexamethasone alone or hydrocortisone plus DOCA exhibited a significant elevation in the olfactory detection threshold for both odorants without any observable structural alteration of the olfactory tissue using light microscopy. On the other hand, neither DOCA, hydrocortisone alone, nor any of the vehicles used in the study significantly altered the olfactory function of the dogs. The results show that Cushing's syndrome can be experimentally produced in dogs using exogenous steroids and that this condition diminishes the olfactory capability of the dog without producing classical signs of the disease.

Techniques for venous blood sampling from the white pekin duck.

Common sites for blood sampling in the pekin duck and other avian species include the basilic vein, jugular vein, superficial plantar metatarsal vein, heart, and occipital sinus. The use of each of these sites is described and/or illustrated. In the present study using the pekin duck, the superficial plantar metatarsal vein proved most satisfactory for collecting repeated samples (every 5 minutes for 30 minutes) with minimal trauma to the duck.

Baseline hematologic, endocrine, and clinical chemistry values in ducks and roosters.

Venous blood samples were collected at 3-day intervals for a total of six samples from each of five adult male pekin ducks and five adult Ross roosters. Twenty biochemical, six hematologic, and three endocrine determinations were performed on each blood or serum sample collected. The data obtained provide reference values for future studies of avian species and illustrate the utility of an automated clinical chemistry analyzer in assessing multiple serum biochemistry values in small sample volumes obtained from birds.

Preservative effect of aprotinin on canine plasma immunoreactive adrenocorticotropin concentrations.

The susceptibility of adrenocorticotropin (ACTH) in canine blood and plasma to enzymatic degradation has limited the availability of endogenous ACTH assay for veterinary use. This study examined if a proteinase (enzyme) inhibitor, aprotinin, mixed with blood at the time of collection, would limit the loss of immunoreactive (IR) ACTH from canine plasma stored at various temperatures. Blood was collected from laboratory-maintained dogs or dogs with hyperadrenocorticism and placed into EDTA-containing tubes in the presence or absence of aprotinin. Plasma obtained was stored for 4 d at temperatures ranging from -86 degrees C to room temperature (22 degrees C). Results showed that addition of aprotinin preserved IR-ACTH concentrations in plasma stored for 4 d at temperatures < or = 4 degrees C, or in unfrozen plasma stored inside insulated shipping containers containing frozen refrigerant packs. Plasma collected with aprotinin and stored at 22 degrees C showed a slight (17-23%) but significant (P < 0.05) decline in IR-ACTH. Unfrozen plasma collected without aprotinin showed significant (P < 0.05) loss of IR-ACTH during storage under identical conditions. These data indicate that aprotinin has a profound preservative effect upon canine plasma IR-ACTH and that it may be possible to submit unfrozen samples collected with this inhibitor to appropriate reference laboratories for analysis of IR-ACTH.

Effects of parachlorophenylalanine, quipazine and cyproheptadine on growth hormone and adrenocorticotropin secretion in steers.

Adrenergic and perhaps dopaminergic neurons provide inhibitory regulation of growth hormone (GH) secretion in ruminants. This suggests that either serotonergic or other neurons regulate the stimulatory release of GH. The nature of neurotransmitter control of adrenocorticotropin (ACTH) secretion in ruminants has not been determined. Parachlorophenylalanine (PCPA; serotonin synthesis inhibitor), quipazine (serotonin receptor agonist) and cyproheptadine (serotonin receptor antagonist) were utilized in Holstein steers to determine whether serotonin receptors mediate stimulatory actions on GH and ACTH secretion. PCPA (100 mg/kg BW) administered each day at 1900 hr for three successive days did not alter mean GH concentrations, amplitude of GH peaks, nor the number of GH peaks. Likewise, PCPA altered none of these parameters for ACTH. Quipazine injected iv at .1 or .5 mg/kg BW increased plasma GH (P less than .05) and ACTH (P less than .001) concentrations. There was a dose effect of quipazine on both GH (P less than .05) and ACTH (P less than .0001) secretion. Pretreatment of steers with cyproheptadine (.06 and .6 mg/kg BW) reduced the stimulation of GH by quipazine (P less than .0001) and decreased basal GH concentrations (P less than .0004). Cyproheptadine at .06 mg/kg BW did not alter quipazine effects on ACTH, however, the higher dose decreased the peak ACTH response (P less than .02) to quipazine. Studies with quipazine and cyproheptadine indicated that serotonergic mechanisms are likely involved in the regulation of GH and ACTH secretion in steers.

Reduced growth of calves and its reversal by use of anabolic agents.

Disease has profound effects on the immune system, endocrine system, and on the growth process. Since diseases are catabolic to the animal, there is current interest in the possible role of anabolic hormones to counter the effects of disease in general and minimize the effects of a disease process on growth and development. A number of anabolic hormones, such as growth hormone (GH) and estradiol + progesterone (EP), have been studied for their role in enhancing growth and stimulating immune function and are thus candidates for hormonal intervention in disease processes. GH has been shown to be effective in countering some of the deleterious effects of endotoxemia but was ineffective in a parasitic disease model. Studies with EP have shown similar success with both endotoxemia and a parasitic disease model. Moreover, GH and EP do not share a common mechanism of action, suggesting that the effects are not simply due to anabolic actions. While the mechanism of action of GH in endotoxemia has been examined, the effects of EP are via an unknown mechanism, possibly by inhibition of IL-I action or inhibition of nitric oxide overproduction.

The effects of ovarian hormones and ACTH on uterine defense to Corynebacterium pyogenes in cows.

Ovariectomized cows were treated with either estrogen, progesterone or adrenogorticotropic hormone (ACTH). Each cow's uterus was inoculated with 1x10(6)Corynebacterium pyogenes organisms. The cows were evaluated by rectal examination for signs of uterine infection. Peripheral leukocytic phagocytosis was determined by chemiluminescence at the beginning (Day 4) and end (Day 21) of the experiment. Uterine cultures were obtained at the end. None of the estrogen-treated cows developed signs of uterine infection, but all the other cows did develop uterine disease. All the infected cows showed clinical improvement at the experimental end (Day 21). There were no differences between groups for leukocytic phagocytosis on Day 4, but on Day 21, values for progesterone-treated and control cows were similar but greater than those for estrogen or ACTH-treated cows, which were similar. Leukocytic phagocytosis values for all cows were lower on Day 21 than on Day 4. Most of the estrogen- and ACTH-treated cows had negative intrauterine cultures on Day 21 while most of controls and progesterone-treated cows had positive cultures.

Thyroidal and prolactin secretion in agalactic mares.

A study was designed to examine serum concentrations of prolactin (PRL) and iodothyronines before and after thyrotropin releasing hormone (TRH) administration to agalactic (n = 26) and normally (n = 8) lactating mares. Two mg TRH was given intramuscularly (i.m.) twice daily on Day 1 (day of delivery) through Day 5. Jugular venous blood was collected on Days 1 and 5 before TRH (time 0) and at 1 and 3 h post-TRH. Basal serum concentrations of thyroxin (T(4)) were different (P < 0.05) on Day 1 (1.87 vs 1.37 mug/dl) and Day 5 (1.72 vs 1.13 mug/dl) in the normal mares and agalactic mares, respectively. There was no difference in the T(4) response to TRH. While basal serum concentrations of triiodothyronine (T(3)) were not different, agalactic mares responded with greater (P < 0.05) serum concentrations T(3) to TRH on Day 1. Following linear regression of the PRL response to TRH, slope of the lines between groups did not differ; however, elevations were significantly (P < 0.05) greater (1.79 vs 1.28 ng/ml) in control mares compared with agalactic mares, respectively, on Day 1.at 1 h post-TRH. A similar difference existed at time 0 and 1 h on Day 5. Consequently, agalactic mares had reduced basal serum T(4) values; the PRL data leads us to suggest that secretion of this hormone may be insufficient in agalactic mares.