The hypothalamic-pituitary-adrenocortical (HPA) axis was studied in 8 healthy cats after administration of supraphysiologic doses of methylprednisolone (MP). Ovine corticotropin-releasing hormone (oCRH) administration increased cortisol and adrenocorticotropic hormone (ACTH) concentrations. Significant (P < 0.05) suppression of cortisol and a trend toward suppression of ACTH was observed after 1 week of MP administration. The HPA axis quickly recovered from suppressive effects of MP 1 week after administration of the steroid was discontinued. Side effects of oCRH administration were minimal in 7 cats; however, 1 cat had a severe hypotensive reaction. Clinical abnormalities were not associated with MP administration. The HPA axis was suppressed by supraphysiologic doses of MP in all treated cats that lacked clinical signs consistent with iatrogenic HPA axis suppression. Despite the relatively active pars intermedia in cats, compared with human beings and dogs, feedback of MP on the HPA axis resulted in similar trends in oCRH-stimulated ACTH and cortisol concentrations as observed in human beings and dogs. Lack of consistent correlation between ACTH and cortisol concentrations was observed in 3 cats and possibly was related to the active pars intermedia in the cat.

Duration and magnitude of hypothalamic-pituitary-adrenal axis suppression caused by daily oral administration of a glucocorticoid was investigated, using an anti-inflammatory dose of prednisone. Twelve healthy adult male dogs were given prednisone orally for 35 days (0.55 mg/kg of body weight, q 12 h), and a control group of 6 dogs was given gelatin capsule vehicle. Plasma cortisol (baseline and 2-hour post-ACTH administration) and plasma ACTH and cortisol (baseline and 30-minutes post corticotropin-releasing hormone [CRH] administration) concentrations were monitored biweekly during and after the 35-day treatment period. Baseline plasma ACTH and cortisol and post-ACTH plasma cortisol concentrations were significantly (P < 0.05) reduced in treated vs control dogs after 14 days of oral prednisone administration. By day 28, baseline ACTH and cortisol concentrations remained significantly (P < 0.05) reduced and reserve function was markedly (P < 0.0001) reduced as evidenced by mean post-CRH ACTH, post-CRH cortisol, and post-ACTH cortisol concentrations in treated vs control dogs. Two weeks after termination of daily prednisone administration, significant difference between group means was not evident in baseline ACTH or cortisol values, post-CRH ACTH or cortisol values, or post-ACTH cortisol values, compared with values in controls. Results indicate complete hypothalamic-pituitary-adrenal axis recovery 2 weeks after oral administration of an anti-inflammatory regimen of prednisone given daily for 5 weeks.

Veterinarians use flumequine (FLU) widely but its toxicological effects are still unclear.

Veterinarians use flumequine (FLU) widely but its toxicological effects are still unclear. FLU doses of 53, 200, or 750 mg/kg were administered orally for six weeks to pubertal male rats for evaluation of their toxicity. Weight gain was poorer after seven days of exposure to FLU 750, but relative weights of the brain, adrenal and thyroid glands, and testes were notably higher. Haematological and lipid profile parameters, cardiac markers, and inorganic phosphate significantly increased in the FLU 750 group. Blood glucose, oestradiol and serum concentrations of immunoglobulins G (IgG) and E (IgE) significantly decreased after treatment. The levels of interleukins 10 (IL-10) and 6 (IL-6) fell significantly in the FLU 200 and FLU 750 groups. Cytochrome P450, family 1, subfamily A, polypeptide 1 (CYP1A1) and cyclooxygenase-2 (Cox-2) expression amplified after treatment. Serum levels of free triiodothyronine (fT3) and free thyroxine (fT4) reduced in the FLU 200 and FLU 750 groups without changes in total T3 or T4 level. All doses of FLU significantly depressed concentrations of thyroid-stimulating hormone (TSH) and testosterone. Histopathology of thyroid glands from rats treated with FLU 750 showed degeneration and depletion of thyroid follicular epithelial cells. Expression of 8-hydroxydeoxyguanosine (8-OHdG) was increased in a dose-dependent manner in the brain, but decreased in the testes. Expression of CYP1A1 increased in the adrenal and pituitary glands. The results of this study suggest that the toxicity of FLU in rats is an effect of its disruptive influence on the pituitary-thyroid hormonal system and on the dysfunction of the immune system.

Objective-To determine the effects of stress in cats with feline idiopathic cystitis (FIC) by evaluating bladder permeability, sympathetic nervous system function, and urine cortisol:creatinine (C:Cr) ratios during periods of stress and after environmental enrichment. Design-Prospective study. Animals-13 cats with FIC and 12 healthy cats. Procedure-Cats subjected to an acute-onset moderate stressor for 8 days received IV injections of fluorescein. Serum fluorescein concentrations were determined and compared with those of controls to evaluate bladder permeability, and urine C:Cr ratios were compared to evaluate function of the hypothalamic-pituitary-adrenal (HPA) axis. Plasma catecholamine concentrations were analyzed in a subset of cats. After 8 days of moderate stress, cats were moved to an enriched environment, and tests were repeated after 21 days. Results-Serum fluorescein concentrations were significantly higher in cats with FIC at all time points. In the cats in which plasma catecholamine concentrations were determined, concentrations of dihydroxyphenylalanine, norepinephrine, and dihyroxyphenylglycol were significantly higher in cats with FIC at all time points, whereas no differences in urine C:Cr ratio between groups were observed. Conclusion and Clinical Relevance-Cats with FIC appeared to have altered bladder permeability, most notably during the period of initial stress. The increase in plasma dihydroxyphenylalanine concentration suggests that there may be stress-induced increase in the activity of tyrosine hydroxylase, which catalyzes the rate-limiting step in catecholamine synthesis. In contrast, no effects of stress on C:Cr ratios were observed, which suggests there was dissociation between the sympathetic nervous system and HPA-axis responses to stress.

We measured immunoreactive (IR) plasma concentrations of the proopiomelanocortin (POMC)-derived. peptides (adrenocorticotropic hormone [ACTH]; beta-endorphin/beta-lipotropin [beta END/beta LPH]; and alpha-melanocyte stimulating hormone [alpha MSH]) and of cortisol in 100 clinically normal cats. Median plasma concentration of IR-ACTH was 2.7 pmol/L (range, less than or equal to 1.1 to 22 pmol/L), of beta END/beta LPH was 28 pmol/L (range, 3.8 to 130 pmol/L), of alpha MSH was 36 pmol/L (range, less than or equal to 3.6 to 200 pmol/L), and of cortisol was 35 nmol/L (range, 5 to 140 nmol/L). Plasma concentrations of IR-ACTH, alpha MSH, and beta END/beta LPH were at or below the assay sensitivity in 34, 3, and 0% of the cats, respectively. We did not detect a correlation between plasma concentrations of IR-ACTH and beta END/beta LPH (r = 0.23) or between plasma concentrations of IR-ACTH and alpha MSH (r = 0.19). However, there was a significant (P < 0.001) correlation between plasma concentrations of IR-beta END/beta LPH and alpha MSH (r = 0.81). There was not a significant correlation between plasma concentration of cortisol and plasma concentration of any of the IR-POMC peptides. High plasma concentrations of IR-alpha MSH and beta END, POMC peptides secreted predominantly by melanotrophs in other species, indicate that clinically normal cats have an actively secreting pars intermedia. Although the beta END/beta LPH assay used in this study measures the pars distalis-derived peptide beta-LPH, as well as beta END itself, over 95% of the IR-beta END/beta LPH activity in feline plasma containing high concentrations of alpha MSH, but low concentrations of IR-ACTH, was found to coelute with human beta END on gel filtration chromatography. In contrast to the high plasma concentrations of IR-alpha MSH and beta END/ beta LPH, many cats had low to undetectable concentrations of IR-ACTH, a peptide secreted predominantly by pars distalis corticotrophs. The pattern of plasma POMC peptide concentrations found in cats is similar to that reported in rats, but is markedly different from that reported in dogs, in which the secretion of pars intermedia POMC peptides is normally low.

Pituitary cells, collected from five healthy dogs, were cultured and treated with various doses of ovine corticotropin-releasing hormone (CRH), arginine vasopressin (AVP), oxytocin (OT), or angiotensin II (AII) to determine which of these hypothalamic peptides affected adrenocorticotropin (ACTH) secretion. Of the 4 peptides, only CRH significantly increased ACTH secretion from cultured canine anterior pituitary cells. The lowest dose of CRH tested, 0.01 nM, significantly stimulated ACTH release. Co-addition of AVP, OT, or AII with CRH did not increase ACTH secretion beyond that caused by addition of CRH alone. Similarly, neither co-addition of AVP with OT, AVP with AII, or OT with AII significantly stimulated ACTH secretion. These results support a role for CRH in the physiologic regulation of ACTH secretion from the canine anterior pituitary, but do not support regulatory roles for AVP, OT, or AII.

Duration and magnitude of hypothalamic-pituitary-adrenal axis suppression caused by daily oral administration of a glucocorticoid was investigated, using an anti-inflammatory dose of prednisone. Twelve healthy adult male dogs were given prednisone orally for 35 days (0.55 mg/kg of body weight, q 12 h), and a control group of 6 dogs was given gelatin capsule vehicle. Plasma cortisol (baseline and 2-hour post-ACTH administration) and plasma ACTH and cortisol (baseline and 30-minutes post corticotropin-releasing hormone [CRH] administration) concentrations were monitored biweekly during and after the 35-day treatment period. Baseline plasma ACTH and cortisol and post-ACTH plasma cortisol concentrations were significantly (P < 0.05) reduced in treated vs control dogs after 14 days of oral prednisone administration. By day 28, baseline ACTH and cortisol concentrations remained significantly (P < 0.05) reduced and reserve function was markedly (P < 0.0001) reduced as evidenced by mean post-CRH ACTH, post-CRH cortisol, and post-ACTH cortisol concentrations in treated vs control dogs. Two weeks after termination of daily prednisone administration, significant difference between group means was not evident in baseline ACTH or cortisol values, post-CRH ACTH or cortisol values, or post-ACTH cortisol values, compared with values in controls. Results indicate complete hypothalamic-pituitary-adrenal axis recovery 2 weeks after oral administration of an anti-inflammatory regimen of prednisone given daily for 5 weeks.

To determine the effects of long-term thyroxine treatment, histomorphometric analysis was performed on the pituitary and thyroid glands of healthy dogs, dogs treated for 9 weeks with a replacement dose of L-thyroxine, and dogs at 6 weeks after cessation of thyroxine treatment. In treated dogs, the volume density of thyrotropes decreased during thyroxine treatment and increased 6 weeks after cessation of treatment, compared with thyrotropes of healthy nontreated dogs. The activity of the thyroid gland was decreased in dogs during thyroxine treatment, as evidenced by decreases in epithelial volume density, epithelial height, and follicular area, and increase in colloid volume density, compared with thyroid gland activity in nontreated dogs. After cessation of thyroxine treatment, the thyroid gland had decreased colloid area, follicular area, and epithelial volume density, and increased interstitial volume density, compared with the thyroid gland of healthy nontreated dogs. Thyroxine treatment resulted in suppression of pituitary thyrotropes and thyroid follicular activity.