Jack W. Oliver

Physiological Manifestations of Endophyte Toxicosis in Ruminant and Laboratory Species

Fescue alkaloid intake by cattle results in adverse metabolic effects that cause billion dollar losses annually to livestock production in the U.S. alone (Bacon et al., 1977; Garner and Cornell, 1978; Bush et al., 1979; Hoveland et al., 1980; Hemken, et al., 1981; Robbins, 1983; Wallner et al., 1983; Ball, 1984; Jackson et al., 1984ab; Stuedemann et al., 1985; Fribourg et al., 1991, 1995; Hoveland, 1991, 1993; Cross et al., 1995; Porter and Thompson, 1992; Strickland et al., 1993; Paterson et al., 1995), with the fescue toxicosis syndrome described as the major grass-induced toxicosis in the country (Cheeke, 1995). These estimates do not reflect losses attributable to the same alkaloids found in ergotized grains and grasses (Bacon et al., 1986, 1995; Coppock et al., 1989). Grasslands make up an increasing part of the world-wide ecosystem (Clay, 1991, 1993ao, 1994; Siegel and Bush, 1994; Hume, 1993), and endophytic fungi correspondingly infect a larger proportion of the grasslands each year. The presence of the endophyte of tall fescue in several countries gives the fescue toxicosis problem global significance (Siegel et al., 1984; Latch et al., 1984, 1987; Fletcher et al., 1990, 1993). For additional perspectives of important endophyte-infected forage relationships to animals, several reviews can be consulted (Read and Camp, 1986; Bacon, 1993, 1995; Buckner et al., 1979; Stuedemann and Hove-land, 1988; Porter and Thompson, 1992; Strickland et al., 1993; Thompson and Stuedemann 1993; Stuedemann and Thompson, 1993; Schmidt and Osborn, 1993; Prestidge, 1993; Thompson and Garner, 1994; Spiers et al., 1995b; Paterson et al., 1995; Porter, 1994, 1995; Cheeke, 1995; Joost, 1995, Cross et al., 1995).

Steroid hormone concentration profiles in healthy intact and neutered dogs before and after cosyntropin administration

The purpose of this study was to determine steroid hormone concentration profiles in healthy intact and neutered male and female dogs. Seventeen intact female dogs, 20 intact male dogs, 30 spayed female dogs, and 30 castrated male dogs were used in this study. Serum samples were collected before and 1h after cosyntropin administration, and serum concentrations were determined for cortisol, progesterone, 17-OH progesterone (17-OHP), dehydroepiandrosterone sulfate (DHEAS), androstenedione, testosterone, and estradiol. Intact male dogs had greater concentrations of DHEAS, androstenedione, and testosterone. Intact female dogs had greater concentrations of progesterone. There was no significant difference in estradiol concentration among the four groups. Intact male dogs had lower concentrations of cortisol post-stimulation. DHEAS and testosterone did not increase in response to ACTH in intact males, and estradiol concentrations did not increase in response to ACTH in any group. Results from this study will enhance interpretation of suspected adrenal and/or gonadal disorders of dogs. Because estradiol concentrations were similar in all groups of dogs, measuring estradiol may not be a useful diagnostic test. Cortisol concentrations for intact male dogs with hyperadrenocorticism may be lower than those of female or neutered dogs.

Effect of a single dose of dexamethasone on glucose homeostasis in healthy horses by using the combined intravenous glucose and insulin test.

Sustained dexamethasone administration to horses results in insulin resistance, which may predispose them to laminitis. A single dose of dexamethasone is commonly used as a diagnostic aid, yet the effect of a single dose of dexamethasone on glucose homeostasis in horses is not well defined. The objective of this study was to characterize the change in glucose dynamics over time in response to a single dose of dexamethasone. A combined glucose-insulin tolerance test (CGIT) was performed on 6 adult geldings before and at 2, 24, and 72 h postdexamethasone (40 microg/kg of BW, i.v.); a minimum of 1 wk of rest was allowed between treatments. Before any treatment, the CGIT resulted in a hyperglycemic phase followed by a hypoglycemic phase. Dexamethasone affected glucose dynamics in 3 ways: 1) at 2 h, dexamethasone shortened the ascending branch of the negative phase (P < 0.001) of the test, indicating moderate insulin resistance; 2) at 24 h, dexamethasone impaired glucose clearance by extending the positive phase and eliminating the negative phase while insulin was elevated before the CGIT, indicating a decreased response to insulin; and 3) at 72 h, dexamethasone caused a deeper nadir value (P < 0.001) compared with predexamethasone, indicating an increased response to insulin. It was concluded that dexamethasone decreased the response to insulin as early as 2 h and maximally at 24 h. At 72 h, dexamethasone caused an increased response to insulin, which was unexpected.

Vasoconstrictive effects of tall fescue alkaloids on equine vasculature

Summary The in vitro vasoconstrictive effects of equine arteriovenous tissues to alkaloids found in Acremonium coenophialum-infested fescue grass (ergotamine tartrate, ergonovine maleate, and N-acetyl loline) were compared to those of various biogenic amines, including norepinephrine, phenylephrine, BHT-920, and serotonin. In this initial study, both the loline and the ergot compounds were vasoactive, although the contractile effect was less than that of the biogenic amine compounds. The study demonstrates the potential for decreased perfusion of peripheral tissues in horses consuming A. coenophialum-infested fescue grass or hay.

Effects of Leuprolide Acetate on Selected Blood and Fecal Sex Hormones in Hispaniolan Amazon Parrots (Amazona ventralis)

Abstract The luteinizing hormone–releasing hormone agonist leuprolide acetate is used commonly to manage reproductive problems in pet birds. To determine the effect of leuprolide acetate on plasma and fecal hormone levels in a psittacine species, a single 800 µg/kg dose of the 30-day depot form of leuprolide acetate was administered IM in 11 healthy, nonbreeding adult Hispaniolan Amazon parrots (Amazona ventralis), and plasma and fecal hormone levels were measured before and after leuprolide administration. At pooled baseline to 21 days postleuprolide acetate administration, sample collection day was significantly associated with plasma 17β-estradiol and androstenedione levels and fecal 17β-estradiol levels (evaluated in females only). Both plasma androstenedione and plasma 17β-estradiol levels decreased significantly from baseline to a nadir at 7 days postleuprolide acetate administration but did not differ significantly 14 days later from that nadir or from pooled baseline samples, suggesting that the effect of leuprolide on hormone levels remained about 2 weeks. Fecal 17β-estradiol levels increased significantly from the nadir at 7 days postleuprolide to 21 days postleuprolide administration, with trends of the level at 21 days postleuprolide being higher than the pooled baseline level and of decreasing levels from pooled baseline to 7 days postleuprolide administration. Plasma luteinizing hormone and fecal testosterone levels did not change significantly from baseline levels after leuprolide administration over the 2-day period. No significant correlations were found between plasma hormone and fecal hormone levels. These results suggest that measurement of plasma androstenedione, plasma 17β-estradiol, and fecal 17β-estradiol levels might be useful in assessing the effects of 30-day depot leuprolide acetate in Hispaniolan Amazon parrots.

Effects of dietary soy isoflavones on health, steroidogenesis, and thyroid gland function in dogs.

OBJECTIVE To evaluate the effect of a soy-based diet on general health and adrenocortical and thyroid gland function in dogs. Animals-20 healthy privately owned adult dogs. PROCEDURES In a randomized controlled clinical trial, dogs were fed a soy-based diet with high (HID; n = 10) or low (LID; 10) isoflavones content. General health of dogs, clinicopathologic variables, and serum concentrations of adrenal gland and thyroid gland hormones were assessed before treatment was initiated and up to 1 year later. Differences between groups with respect to changes in the values of variables after treatment were assessed by means of a Student t test (2 time points) and repeated-measures ANOVA (3 time points). RESULTS No differences were detected between the 2 groups with respect to body condition and results of hematologic, serum biochemical, and urine analyses. Most serum concentrations of hormones did not change significantly after treatment, nor were they affected by diet. However, the mean change in serum concentration of total thyroxine was higher in the HID group (15.7 pmol/L) than that in the LID group (-1.9 pmol/L). The mean change in estradiol concentration after ACTH stimulation at 1 year after diets began was also higher in the HID group (19.0 pg/mL) than that in the LID group (-5.6 pg/mL). CONCLUSIONS AND CLINICAL RELEVANCE Phytoestrogens may influence endocrine function in dogs. Feeding soy to dogs on a long-term basis may influence results of studies in which endocrine function is evaluated, although larger studies are needed to confirm this supposition.

Hyperphosphatasemia and concurrent adrenal gland dysfunction in apparently healthy Scottish Terriers

OBJECTIVE To determine causes of hyperphosphatasemia (high serum alkaline phosphatase [ALP] activity) in apparently healthy Scottish Terriers. DESIGN Prospective case-controlled study. ANIMALS 34 apparently healthy adult Scottish Terriers (17 with and 17 without hyperphosphatasemia). PROCEDURES Serum activities for 3 isoforms (bone, liver, and corticosteroid) of ALP were measured. Concentrations of cortisol, progesterone, 17-hydroxyprogesterone, androstenedione, estradiol, and aldosterone were measured before and after cosyntropin administration (ie, ACTH; 5 microg/kg [2.27 microg/lb], IM). Liver biopsy specimens from 16 dogs (11 with and 5 without hyperphosphatasemia) were evaluated histologically. RESULTS In dogs with hyperphosphatasemia, the corticosteroid ALP isoform comprised a significantly higher percentage of total ALP activity, compared with the percentage in dogs without hyperphosphatasemia (mean +/- SE, 69 +/- 5.0% and 17 +/- 3.8%, respectively). In 6 dogs with hyperphosphatasemia, but none without, serum cortisol concentrations exceeded reference intervals after ACTH stimulation. Six dogs with and 15 without hyperphosphatasemia had increased concentrations of >or = 1 noncortisol steroid hormone after ACTH stimulation. Serum ALP activity was correlated with cortisol and androstenedione concentrations (r = 0.337 and 0.496, respectively) measured after ACTH stimulation. All dogs with and most without hyperphosphatasemia had abnormal hepatocellular reticulation typical of vacuolar hepatopathy. Subjectively, hepatocellular reticulation was more severe and widespread in hyperphosphatasemic dogs, compared with that in nonhyperphosphatasemic dogs. CONCLUSIONS AND CLINICAL RELEVANCE Hyperphosphatasemia in apparently healthy Scottish Terriers was most likely attributable to hyperadrenocorticism on the basis of exaggerated serum biochemical responses to ACTH administration and histologic hepatic changes, but none of the dogs had clinical signs of hyperadrenocorticism.

Blood steroid concentrations in domestic Mongolian horses.

Traditionally, analysis of blood cortisol alone has been used to evaluate adrenal function. Currently, multisteroid analyses are considered more informative than analysis of a single hormone to assess adrenal function. The objective of the present research was to create a database for steroid reference values for domestic Mongolian horses. Seven adrenal steroid levels were determined in the blood of 18 colts, 34 stallions, 25 geldings, 17 fillies, and 29 mares. Results were as follows (lowest and highest group median, in nanograms per milliliter): progesterone: <0.030 (fillies), 4.30 (mares), and 0.070 (all horses); 17-OH-progesterone: 0.070 (colts), 0.520 (mares), and 0.110 (all horses); androstenedione: 0.101 (colts), 0.256 (stallions), and 0.181 (all horses); testosterone: <0.040 (mares, stallions, and fillies), 0.040 (geldings and colts), and <0.40 (all horses); estradiol: 0.066 (stallions), 0.093 (fillies), and 0.085 (all horses); cortisol: 23.040 (colts), 70.210 (geldings), and 50.770 (all horses); and aldosterone: 0.018 (colts), 0.297 (geldings), and 0.191 (all horses). Overall medians indicate that cortisol (98.70%) is the predominant steroid, followed by aldosterone (0.37%), androstenedione (0.35%), 17-OH-progesterone (0.21%), estradiol (0.17%), progesterone (0.14%), and testosterone (0.06%). This information provides adrenal and gonadal steroid reference concentrations to assist in physiological characterization and diagnosis of endocrine disorders in domestic Mongolian horses.

Effect of combined lignan phytoestrogen and melatonin treatment on secretion of steroid hormones by adrenal carcinoma cells

OBJECTIVE To investigate the in vitro effect of the combination of lignan enterolactone (ENL) or lignan enterodiol (END) with melatonin on steroid hormone secretion and cellular aromatase content in human adrenal carcinoma cells. SAMPLE Human adrenocortical carcinoma cells. PROCEDURES Melatonin plus ENL or END was added to cell culture medium along with cAMP (100μM); control cells received cAMP alone. Medium and cell lysates were collected after 24 and 48 hours of cultivation. Samples of medium were analyzed for progesterone, 17-hydroxyprogesterone, androstenedione, aldosterone, estradiol, and cortisol concentration by use of radioimmunoassays. Cell lysates were used for western blot analysis of aromatase content. RESULTS The addition of ENL or END with melatonin to cAMP-stimulated cells (treated cells) resulted in significant decreases in estradiol, androstenedione, and cortisol concentrations at 24 and 48 hours, compared with concentrations in cells stimulated with cAMP alone (cAMP control cells). The addition of these compounds to cAMP-stimulated cells also resulted in higher progesterone and 17-hydroxyprogesterone concentrations than in cAMP control cells; aldosterone concentration was not affected by treatments. Compared with the content in cAMP control cells, aromatase content in treated cells was significantly lower. CONCLUSIONS AND CLINICAL RELEVANCE The combination of lignan and melatonin affected steroid hormone secretion by acting directly on adrenal tumor cells. Results supported the concept that this combination may yield similar effects on steroid hormone secretion by the adrenal glands in dogs with typical and atypical hyperadrenocorticism.