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ORIGINAL ARTICLE
Year : 2016  |  Volume : 13  |  Issue : 3  |  Page : 136-139

Effect of prednisolone on thyroid and gonadotrophic hormones secretion in male domestic rabbits


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 Publication27-Oct-2016

Correspondence Address:
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

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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-0354.193135

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  Abstract 

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 2020 Aug 8];13:136-9. Available from: http://www.thetrp.net/text.asp?2016/13/3/136/193135


  Introduction Top


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. [1] 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. [2] Two examples of synthetic glucocorticoids that are in common clinical use are prednisolone and dexamethasone. [3] 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. [4] A similar reduction in basal circulating values of T 4 and T 3 was observed in dogs given prednisone. [5],[6],[7] In rabbits, serum T 4 and T 3 levels declined after injection of adrenocorticotrophic hormone. [8] Glucocorticoids also have an effect on gonadotrophic hormones secretion. Basal levels of luteinizing hormone (LH) were suppressed in patients with Cushing's syndrome [9] and bulls given dexamethasone. [10] Short-term of high dose of dexamethasone or paramethasone acetate administration decreased basal levels of LH in women with normal menstrual cycle. [11] An excess of endogenous and exogenous glucocorticoids causes many biochemical endocrine effects. [7],[12],[13],[14],[15] 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 Top


Experimental animals

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 sampling

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.

Assay procedure

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.

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 (SAS Institute Inc., Cary, NC, USA).


  Results Top


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 Top


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 [16] and healthy dogs [6] 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. [7] 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. [15] 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. [6],[7],[15] 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. [6],[7],[15] 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 [4] 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. [17],[18] 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. [18] 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. [19] 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 [11] 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. [11] Moreover, another study [20] 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. [20] It has been observed that patients with Cushing's disease have suppressed basal levels of LH and FSH and diminished gonadotropin responses to GnRH. [9] In addition, the current result of LH reduction due to prednisolone treatment is in agreement with the result of [10] 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. [20] The same authors [20] 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 [10] and dogs. [15] 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.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
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Visser TJ, Lamberts SW. Regulation of TSH secretion and thyroid function in Cushing's disease. Acta Endocrinol (Copenh) 1981;96:480-3.  Back to cited text no. 16
    
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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.  Back to cited text no. 20
    



 
 
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