|Year : 2016 | Volume
| Issue : 3 | Page : 136-139
Effect of prednisolone on thyroid and gonadotrophic hormones secretion in male domestic rabbits
Barakat Elmahdi1, M Hassan2, Sabry Mohamed El-Bahr3
1 Department of Chemistry, College of Science, King Faisal University, Saudi Arabia; Department of Biochemistry, Faculty of Veterinary Medicine, University of Khartoum, Khartoum, Sudan
2 Department of Biochemistry, Faculty of Veterinary Medicine, University of Khartoum, Khartoum, Sudan
3 Department of Physiology, Biochemistry and Pharmacology (Biochemistry), College of Veterinary Medicine and Animal Resources, King Faisal University, Saudi Arabia; Department of Biochemistry, Faculty of Veterinary Medicine, Alexandria University, Egypt
|Date of Web Publication||27-Oct-2016|
Sabry Mohamed El-Bahr
Department of Physiology, Biochemistry and Pharmacology (Biochemistry), College of Veterinary Medicine and Animal Resources, King Faisal University, Al-Ahsa, P.O. Box 400, Al-Hofuf 31982
Source of Support: None, Conflict of Interest: None
Context: An excess of endogenous and exogenous glucocorticoids causes many biochemical endocrine effects. Such alterations resulted in erroneous misleading interpretation of laboratory results. Aims: The effect of six intramuscular (I/M) injections of prednisolone on the serum concentrations of thyroxin (T 4 ), triiodothyronine (T 3 ), thyroid stimulating hormone (TSH), and luteinizing hormone (LH) of male domestic rabbits was assessed. Materials and Methods: Ten rabbits were assigned into two equal groups, treated and control groups. The treated group was injected prednisolone 1% at a rate of 2.2 mg/kg body weight every other day for a total of six doses. The control group was injected I/M with an equivalent volume of vehicle solution of prednisolone 1%. Statistical Analysis: All data were presented as mean ± standard error of mean by Student's t-test. All tests were performed using the Statistical Package for Social Science Program. Results: At day 6 of the experiment (after three injections of prednisolone), there were nonsignificant differences (P > 0.5) in serum T 4 , T 3 and TSH concentrations in prednisolone-treated animals compare to control. However, the concentration of serum LH was decreased significantly (P < 0.5) in prednisolone-treated animals compare to control. At day 12 of the experiment (after six injections of prednisolone), there were nonsignificant changes (P > 0.5) in the concentration of TSH in prednisolone-treated animals compare to control whereas the concentrations of serum T 4 , T 3 and LH were decreased significantly (P < 0.5) in prednisolone-treated animals compare to control. Conclusion: Multiple administration of prednisolone was clearly associated with substantial reduction in the concentrations of T 4 and T 3 and reduction of LH concentration without any effect on TSH concentration in serum of domestic rabbits.
Keywords: Luteinizing hormones, prednisolone, rabbits, serum, thyroid hormones
|How to cite this article:|
Elmahdi B, Hassan M, El-Bahr SM. Effect of prednisolone on thyroid and gonadotrophic hormones secretion in male domestic rabbits. Thyroid Res Pract 2016;13:136-9
|How to cite this URL:|
Elmahdi B, Hassan M, El-Bahr SM. Effect of prednisolone on thyroid and gonadotrophic hormones secretion in male domestic rabbits. Thyroid Res Pract [serial online] 2016 [cited 2022 Sep 29];13:136-9. Available from: https://www.thetrp.net/text.asp?2016/13/3/136/193135
| Introduction|| |
Glucocorticoids are potent anti-inflammatory and immunosuppressive agents. They are extensively used in bone marrow transplantation, solid organ transplantation, and treatment of hematological malignancies, rheumatoid arthritis, and chronic pulmonary conditions, e.g., asthma.  However, the adverse metabolic effects are difficult to separate pharmacologically from the therapeutic benefits, making glucocorticoids potent, yet potentially dangerous compounds. They are among the most widely used class of drugs in human and veterinary medicine. It should be recognized that local applications also have similar systemic effects.  Two examples of synthetic glucocorticoids that are in common clinical use are prednisolone and dexamethasone.  Administration of glucocorticoids results in an altered function of the pituitary-thyroid axis in several species. In human, glucocorticoids have been reported to reduce the basal thyroid stimulating hormone (TSH) concentrations, circulating serum thyroxin (T 4 ), and 3, 5, 3-triiodothyronine (T 3 ) concentrations.  A similar reduction in basal circulating values of T 4 and T 3 was observed in dogs given prednisone. ,, In rabbits, serum T 4 and T 3 levels declined after injection of adrenocorticotrophic hormone.  Glucocorticoids also have an effect on gonadotrophic hormones secretion. Basal levels of luteinizing hormone (LH) were suppressed in patients with Cushing's syndrome  and bulls given dexamethasone.  Short-term of high dose of dexamethasone or paramethasone acetate administration decreased basal levels of LH in women with normal menstrual cycle.  An excess of endogenous and exogenous glucocorticoids causes many biochemical endocrine effects. ,,,, Such alterations resulted in erroneous misleading interpretation of laboratory results. Therefore, this study was designed to determine the effects if any, induced by prednisolone on thyroid metabolic hormones, TSH, and LH levels in domestic rabbits.
| Materials and methods|| |
Ten adult apparently healthy domestic male rabbits (Lepus cuniculus) weighing 1.1-1.65 kg were used in the current study. The animals received humane care in accordance with the Guide for the Care and Use of Laboratory Animals. The rabbits were penned singly in wire net cages (60 cm × 60 cm × 60 cm) to avoid social stress. They were provided with adequate ventilation under natural light. The animals were fed equal amounts of fresh lucerne (Medicago sativa) 0.4 kg and sorghum grains (Sorghum vulgare cundatum) 90 g with water available ad libitum. The rabbits were kept for an adaptation period of 2 weeks, so they were accustomed to handling, collection of blood, and experimental conditions.
The experimental procedure
The rabbits (n = 10) were randomly assigned into two equal groups, treated and control groups. The treated group was injected intramuscularly (I/M) with prednisolone 1% (VMD, Belgium) at a rate of 2.2 mg/kg body weight every other day for a total of six doses. The control group was injected I/M with an equivalent volume of vehicle solution of prednisolone 1% (VMD, Belgium).
Blood samples were obtained by venipuncture of the jugular vein using a 24-gauge needle and 5 ml disposable syringe on the days 6 and 12 of the experiment. Blood was then transferred to plain tubes with clot activator and allowed to clot at room temperature for 3 h. The clotted blood was centrifuged at 3000 rpm for 10 min. The separated serum was immediately stored at −20°C until analysis.
Commercial enzyme immunoassay kits of EQUIPAR SRL (Saronno VA, Italy) were used for determination of T 4 (code: 62001), T 3 (code: 61501), TSH (code: 58001), and LH (code: 53001) concentrations.
All data were presented as mean ± standard error of mean by Student's t-test. All tests were performed using the Statistical Package for Social Science Program (SAS Institute Inc., Cary, NC, USA).
| Results|| |
The mean concentrations of serum T 4 , T 3 , TSH, and LH in rabbits given multiple I/M injections of prednisolone (2.2 mg/kg body weight) every alternate day were compared with those of control animals in two separate periods, days 6 and 12, respectively. The concentrations of T 4 and T 3 on the days 6 and 12 of the experiment were presented in [Table 1] and [Table 2], respectively. There was a nonsignificant difference in serum T 4 and T 3 levels between the treated and the control groups on the day 6 of the experiment [Table 1]. However, on the day 12 of the experiment [Table 2], the mean values of T 4 and T 3 were significantly (P < 0.05) reduced in the treated group compare to the control. The mean values of TSH of the treated group was nonsignificantly different compared to that of the control group on the days 6 [Table 1] and 12 [Table 2] of the experiment. Meanwhile, on the days 6 [Table 1] and 12 [Table 2] of the experiment, the mean values of LH of the treated group were significantly (P < 0.05) reduced compared to the control group.
|Table 1: The levels of thyroxin, triiodothyronine, thyroid stimulating hormone, and luteinizing hormone in rabbits treated with prednisolone (2.2 mg/kg body weight) given intramuscular compared to the control on day 6 of the experiment |
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|Table 2: The levels of thyroxin, triiodothyronine, thyroid stimulating hormone, and luteinizing hormone in rabbits treated with prednisolone (2.2 mg/kg body weight) given intramuscular compared to the control on day 12 of the experiment |
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| Discussion|| |
In the present study, multiple administration of prednisolone was clearly associated with substantial reduction in the serum levels of T 4 and T 3 . Similar results had been observed in patients with Cushing's syndrome  and healthy dogs  after the third I/M injection of prednisone 2.2 mg/kg body weight. Reduction in T 4 and T 3 occurred in dogs given oral dose of prednisone 0.55 mg/kg body weight/day after 8 days.  The current findings indicated that the levels of both T 4 and T 3 were nonsignificantly reduced up to the day 6, third injection. It is suggested that, glucocorticoid-induced suppression of T 4 and T 3 levels in a dose-related phenomenon which may also be affected by the route of administration, chemical form of the agent, sex of the subject, doses, and treatment duration.  The significant reduction of peripheral T 4 and T 3 levels in rabbits given prednisolone on the day 12 of the current experiment may attribute to direct effect of glucocorticoid on the thyroid gland resulting in stabilization of lysosomal enzymes. ,, The hydrolysis of colloid by lysosomal enzymes is a prerequisite for thyroid hormone secretion. The stabilizing effect of glucocorticoids on lysosomal membranes could account for the cytoplasmic colloid accumulation as revealed by electron microscopic examination of thyroid tissue of dogs treated with prednisone and subsequent reduction of T 4 and T 3 secretion by inhibition of lysosomal hydrolysis of the colloid in the thyroid follicular cells. ,, In this study, the mean values of TSH were not significantly reduced on the days 6 and 12 of the experiment. This finding disagrees with the study of  who observed a profound reduction in TSH in men given a single dose of betamethasone 8 mg intravenously. The variation is possibly due to the potency of the drug and/or the dose and the route of administration. The explanation for these findings is that low or normal TSH and low thyroid hormones test results represent a typical pattern in ill patients with nonthyroidal illness. , Nonendocrinologists are frequently surprised to find TSH in the normal range in this situation since the pituitary fails to respond adequately to low thyroid hormones concentration.  In clinical practice, this is the greatest challenge in diagnosis of the condition. Glucocorticoids, dopamine, and dobutamine can suppress serum TSH even in patients with overt primary hypothyroidism. Thus, thyroid function testing is best reserved for severely ill patients in whom there is a substantial clinical suspicion of hypothyroidism; otherwise, abnormal results are much more likely to represent false-positive than true-positive findings.  In the present study, the serum levels of LH were significantly decreased on the days 6 and 12 of the experiment. These findings are in agreement with a prior study  in which administration of paramethasone acetate at a dose rate of 5 mg daily to young women with normal menstrual cycles resulted in significantly depressed basal LH levels on the second day of administration. This suppression persisted throughout most of the menstrual cycle.  Moreover, another study  was conducted to determine the effect of short-term administration of high doses of glucocorticoids on LH and follicle stimulating hormone (FSH) secretion and the site of this effect in women with ovulatory cycles. There was a significant reduction in the basal levels of LH and FSH, and the gonadotropins response to gonadotropin-releasing hormone (GnRH) was blunted.  It has been observed that patients with Cushing's disease have suppressed basal levels of LH and FSH and diminished gonadotropin responses to GnRH.  In addition, the current result of LH reduction due to prednisolone treatment is in agreement with the result of  who gave a single dose of 20 mg dexamethasone for each treated bull. The administration of dexamethasone suppressed baseline serum level of LH and blunted LH response to GnRH in healthy women with normal menstrual cycles.  The same authors  reported that, 100 µg of GnRH intravenously on the day 6 of two consecutive menstrual cycles, once with and once without pretreatment with dexamethasone 2 mg/woman orally every 6 h, on the days 2 through 5 of the menstrual cycle suppress the secretion of LH by direct effect on the pituitary and/or by an effect at the hypothalamic level with inhibition of the release of GnRH. Similar explanation for the effect of glucocorticoids on LH has been reported in bulls  and dogs.  Therefore, in the present study, it is suggested that the inhibition of LH secretion in domestic rabbits treated with prednisolone was at the hypothalamic and the pituitary level. The current study indicated that multiple administration of prednisolone was clearly associated with substantial reduction in the concentrations of T 4 and T 3 and reduction of LH concentration without any effect on TSH concentration in serum of domestic rabbits.
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Conflicts of interest
There are no conflicts of interest.
| References|| |
Lionakis MS, Kontoyiannis DP. Glucocorticoids and invasive fungal infections. Lancet 2003;362:1828-38.
Adams HR. Veterinary Pharmacology and Therapeutics. 8 th
ed. Lowa: Blackwell Publishing Company; 2001. p. 649-71.
Laurence DR, Bennett PH, Brown MJ. Clinical Pharmacology. 18 th
ed. London: Livingstone; 1999. p. 599-613.
Azukizawa M, Mori S, Ohta H, Matsumura S, Yoshimoto H, Uozumi T, et al.
Effect of a single dose of glucocorticoid on the diurnal variations of TSH, thyroxine, 3,5,3'-triiodothyronine, 3,3'5'- triiodothyronine and cortisol in normal men. Endocrinol Jpn 1979;26:719-23.
Kemppainen RJ, Peterson ME, Sartin JL. Plasma free cortisol concentrations in dogs with hyperadrenocorticism. Am J Vet Res 1991;52:682-6.
Woltz HH, Thompson FN, Kemppainen RJ, Munnell JF, Lorenz MD. Effect of prednisone on thyroid gland morphology and plasma thyroxine and triiodothyronine concentrations in the dog. Am J Vet Res 1983;44:2000-3.
Kurtdede A, Asti RN, Kurtdede N, Karagul H, Atalay O, Guzel M. Effects of anti-inflammatory and immuuno-suppressive doses of prednisolone on serum triiodothyronine, thyroxine, and free thyroxine concentrations and thyroid morphology in the dog. Rev Méd Vét 2004;155:232-330.
Ramsden DB, Smith TJ, Burr WA, Black EG, Lee JM, Hoffenberg R. Effects of surgical stress and corticotrophin on the peripheral metabolism of thyroid hormones in rabbits. J Endocrinol 1979;82:403-8.
Luton JP, Thieblot P, Valcke JC, Mahoudeau JA, Bricaire H. Reversible gonadotropin deficiency in male Cushing's disease. J Clin Endocrinol Metab 1977;45:488-95.
Chantaraprateep P, Thibier M. Effects of dexamethasone on the responses of luteinizing hormone and testosterone to two injections of luteinizing hormone releasing hormone in young postpubertal bulls. J Endocrinol 1978;77:389-95.
Cortés-Gallegos V, Gallegos AJ, Tovar NB, Cervantes C, Parra A. Effect of paramethasone acetate on ovarian steroids and gonadotropins. I. Normal menstrual cycle. J Clin Endocrinol Metab 1975;41:215-20.
DeNovo RC, Prasse KW. Comparison of serum biochemical and hepatic functional alterations in dogs treated with corticosteroids and hepatic duct ligation. Am J Vet Res 1983;44:1703-9.
Dandona P, Jungle D, Katrak A, Fonseca AV, Havard CWH. Serum pancreatic enzymes increase following prednisolone: Possible evidence of subclinical pancreatitis. Br Med J 1985;291:24.
Meyer DJ, Moriello KA, Feder BM, Fehrer-Sawyer SL, Maxwell AK. Effect of otic medications containing glucocorticoids on liver function test results in healthy dogs. J Am Vet Med Assoc 1990;196:743-4.
Kemppainen RJ, Thompson FN, Lorenz MD, Munnell JF, Chakraborty PK. Effects of prednisone on thyroid and gonadal endocrine function in dogs. J Endocrinol 1983;96:293-302.
Visser TJ, Lamberts SW. Regulation of TSH secretion and thyroid function in Cushing's disease. Acta Endocrinol (Copenh) 1981;96:480-3.
Lindsay RS, Toft AD. Hypothyroidism. Lancet 1997;349:413-7.
Dayan CM. Interpretation of thyroid function tests. Lancet 2001;357:619-24.
Roberts CG, Ladenson PW. Hypothyroidism. Lancet 2004;363:793-803.
Sowers JR, Rice BF, Blanchard S. Effect of dexamethasone on luteinizing hormone and follicle stimulating hormone responses to GnRH and to clomiphene in the follicular phase of women with normal menstrual cycles. Horm Metab Res 1979;11:478-80.
[Table 1], [Table 2]