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Biomedical subjects

M J Fennell

Publications and source records attributed to M J Fennell.

10 recordsLinked to original sources

The suppressive effects of testosterone on growth in young chickens appears to be mediated via a peripheral androgen receptor; studies of the anti-androgen ICI 176,334.

ICI 176,334 is a nonsteroidal anti-androgen that has been shown to selectively block peripheral androgen receptors in rats and is presumed to do so in chickens. In chickens, androgens stimulate secondary sexual characteristics (e.g., comb), but inhibit growth and the immune tissues. The present study examined the effect of dietary ICI 176,334 (5 or 25 mg/kg body weight) on growth in chickens in the presence or absence of testosterone treatment (as 1-cm long silastic implants). Treatments began at 2 wk of age and continued through 6 wk of age. Testosterone alone reduced body growth (average daily gain and shank-toe length, together with weights of the body, skeletal muscle, and the bursa of Fabricius, an immune tissue), and stimulated comb development. At the low dose (5 mg/kg), ICI 176,334 alone had no effect on body growth or organ weight with the exception that comb weight was reduced. At the high dose (25 mg/kg), ICI 176,334 decreased growth (body weight, average daily gain, and shank-toe length) and organ weights (breast muscle, bursa of Fabricius, testis, and comb weights). This effect may represent a toxicity. As might be expected with an anti-androgen, ICI 176,334 (at either 5 or 25 mg/kg) completely suppressed the stimulation of comb growth evoked by testosterone. Similarly, ICI 176,334 (5 mg/kg) overcame, albeit partially, the growth-suppressive effects of testosterone (on body weight, average daily gain, shank-toe length, and breast muscle weight) and also had inhibitory effects on the weights of the testis and bursa of Fabricius. The anti-androgen, ICI 176,334, did not influence the reduction in circulating concentrations of luteinizing hormone occurring after testosterone treatment. The present data are consistent with the growth-suppressive effects of testosterone in chickens being mediated via a peripheral androgen receptor. No effects of either testosterone or ICI 176,334 were observed on circulating concentrations of insulin-like growth factor-I despite the marked changes in growth rate.

Androgen Antagonists↗

Inhibition of growth in chickens by testosterone, 5 alpha-dihydrotestosterone, and 19-nortestosterone.

The growth response of poultry to androgens is ambiguous, with both increases and decreases being reported. This may reflect the use of pharmacological doses. The present study examined the effect of physiological concentrations of androgens on growth of intact male, intact female, and castrated chickens. Physiological concentrations of androgen were attained by subcutaneous silastic implants. In mammals, androgens have both androgenic effects on the reproductive organs and anabolic growth-promoting effects on body and muscle growth. Some androgens, for instance 5 alpha-dihydrotestosterone (5 alpha-DHT) have high androgenic activity (5 alpha-DHT greater than testosterone) but others, e.g., 19-nortestosterone, have high anabolic activities (19-nortestosterone greater than testosterone greater than 5 alpha-DHT). The relative effects of testosterone, 5 alpha-DHT, and 19-nortestosterone on growth were compared in chickens. In young, intact male and female chicks, growth was suppressed by 1.0-cm silastic implants of testosterone and 5 alpha-DHT (5 alpha-DHT greater than testosterone). Castrated chicks were implanted with implants of various sizes (.3, 1.0, and 3.0 cm) containing testosterone, 5 alpha-DHT, or 19-nortestosterone. The androgens inhibited body weight gain: 19-nortestosterone reducing body weight at all three doses, 5 alpha-DHT reducing body weight at the intermediate and high doses, and testosterone tending to reduce body weight only at the high dose. Testosterone (3.0 cm), 5 alpha-DHT (all doses), and 19-nortestosterone (all doses) reduces skeletal growth, as indicated by shank-toe length. In contrast to their growth-suppressing effect, all three steroids exerted an androgenic effect; stimulating comb and wattle development (19-nortestosterone greater than 5 alpha-DHT greater than testosterone). It is concluded that androgens are androgenic but are not anabolic in chickens.

Adipose Tissue↗

Effects of androgen (testosterone, 5 alpha-dihydrotestosterone, 19-nortestosterone) administration on growth in turkeys.

The present studies examined the effect of three androgens, testosterone, a reduced form 5 alpha-dihydrotestosterone (5 alpha-DHT), and the readily aromatizable anabolic androgen, 19-nortestosterone, on growth in male and female turkeys. Growth (body weight, average daily gain, and right breast muscle weight) was increased by testosterone (females), 5 alpha-DHT (males and females), and 19-nortestosterone (males and females). Moreover, both feed:gain ratio and the weight of abdominal adipose tissue was reduced in turkeys treated with testosterone (females), 5 alpha-DHT (males and females), and 19-nortestosterone (females and males). Bursa of Fabricius weights were reduced in androgen-treated male or female turkeys with the decrease following 19-nortestosterone being greater than those observed with either testosterone or 5 alpha-DHT. Androgen treatment had no effect on skeletal growth (as indicated by shank-toe length) or weights of the liver, spleen, or testes. In female turkeys, plasma concentrations of hormones were determined following androgen treatment. No effects were observed on plasma concentrations of insulin-like growth factor-I or luteinizing hormone after any androgen treatment. Testosterone administration was followed by a physiological increase in the plasma concentrations of testosterone. Plasma concentrations of growth hormone were unaffected by either 5 alpha-DHT or 19-nortestosterone but reduced by the high dose of testosterone. The effect of castration on growth in the presence or absence of 19-nortestosterone was also examined. Castration did not depress growth compared with sham-operated controls, but increased adiposity. 19-Nortestosterone increased growth of castrated turkeys, increased muscle weight, and reduced abdominal adipose tissue weight.

Adipose Tissue↗

Influence of androgens on plasma concentrations of growth hormone in growing castrated and intact chickens.

Castrated chicks implanted with testosterone or 5 alpha-dihydrotestosterone (5 alpha-DHT) had circulating concentrations of the respective androgen similar to or less than in sham-operated chicks. In castrated chicks, 5 alpha-DHT or 19-nortestosterone (19-NorT) inhibited growth as indicated by body weight, while testosterone and 5 beta-dihydrotestosterone (5 beta-DHT) were without effect. In intact male or female chicks, growth was inhibited by either testosterone or 5 alpha-DHT but was unaffected by 5 beta-DHT or estradiol-17 beta. Plasma concentrations of luteinizing hormone (LH) were reduced in castrated chicks receiving implants of either testosterone or 19-NorT. Only the highest dose of 5 alpha-DHT depressed the circulating concentration of LH; lower doses of 5 alpha-DHT being without effect. During the first 6 weeks of growth, plasma concentrations of GH were unaffected by most steroid treatments (5 alpha-DHT, 5 beta-DHT, low doses of testosterone, estradiol-17 beta) in castrated or in intact male or in female chicks. Similarly, 19-NorT did not affect plasma concentrations of GH in castrated chicks. The high dose of testosterone, however, depressed plasma concentrations of GH in castrated chicks between 2 and 6 weeks of age. Between 8 and 12 weeks of age, all steroids tested, except 5 alpha-DHT, were without effect on plasma concentrations of GH. Plasma concentrations of GH were increased in 5 alpha-DHT-treated chickens. This effect was observed irrespective of dose of 5 alpha-DHT or whether the androgen was administered to castrated or to intact male or to female chicks.

Androgens↗

Distraction in neurotic and endogenous depression: an investigation of negative thinking in major depressive disorder.

The effects on depressive thinking and depressed mood of a brief, standardized distraction procedure were examined. In low endogenous patients (scoring 3 or less on the Newcastle Diagnosis Scale (NDS)), distraction significantly reduced the frequency of depressing thoughts. Consistent with Beck's cognitive model of depression, these patients were significantly less depressed after distraction than after a control procedure. In high endogenous patients (scoring 4 or more on the NDS), distraction produced less marked reductions in frequency of depressing thoughts, and no significant change in depressed mood. It is suggested that the relationship between negative thinking and depressed mood differs in the two patient groups.

Adolescent↗

Adrenocortical function of the domestic fowl: effects of orchiectomy and androgen replacement.

The effect of orchiectomy and androgen replacement on cockerel adrenocortical function was investigated. Orchiectomized cockerels (2 weeks old) were implanted with Silastic tubing containing various amounts of one of the following steroids: cholesterol, testosterone (T), androstenedione (A4), and 5 alpha-dihydrotestosterone (DHT). Birds were administered additional implants, containing doses of steroids equivalent to those of the initial implants, at 4 and 8 weeks of treatment (i.e., 6 and 10 weeks of age). Sham-operated cockerels administered empty implants served as intact controls for comparison of data. Animals were killed after 10 weeks of treatment (12 weeks old). Trunk plasma corticosterone (B) and plasma T, and B production by collagenase-isolated adrenocortical cells incubated briefly (2 hr) with or without steroidogenic agents were measured by radioimmunoassay. Orchiectomy with implantation of the inert sterol, cholesterol (hereafter referred to as orchiectomy), did not alter plasma B concentrations and did not affect basal cellular B production or cellular B production induced by a maximal steroidogenic concentration of ACTH or that maximally supported by 25-hydroxycholesterol. However, orchiectomy did lower maximal 8-bromo-cyclic AMP-induced B production by 30%. Low-implant doses of A4 (1-cm implant) and T (0.3-cm implant), that maintained comb growth, lowered plasma B concentrations by 24-42%, whereas a high-implant dose of T (3-cm implant) and all implant doses of DHT had no effect on plasma B concentrations. Thus, androgen replacement had different effects on plasma B depending on the type of androgen and the implant dose. In contrast, androgen replacement consistently suppressed basal and maximal ACTH-induced cellular B production regardless of the type of androgen. Furthermore, the degree of suppression was dose-dependent. These results suggest that the differential effect of androgen replacement on plasma B concentrations was due to differences in the clearance of circulating B and/or differences in blood volume. In addition, the present study suggests that in the absence of the testes, androgens are suppressants of adrenocortical cell function in the domestic fowl.

8-Bromo Cyclic Adenosine Monophosphate↗

Effects of distraction on thinking and affect in depressed patients.

Beck's cognitive model of depression suggests that negative cognitions can maintain depression. Thus reducing the frequency of negative cognitions should reduce depression. Consistent with this proposition, in low endogenous patients with primary major depressive disorder, distraction produced fewer depressing thoughts than the control procedure, with corresponding differences in self-report and psychomotor measures.

Affect↗

The cognitions questionnaire: specific thinking errors in depression.

With the development of cognitive models of depression, interest in identifying an enduring cognitive style characteristic of depression-prone individuals has increased. However, empirical evidence for cognitive vulnerability of this kind is as yet sparse. The paper describes the development of a Cognitions Questionnaire (CQ), designed not only to provide an overall measure of depressive cognitive style, but also to assess specific dimensions of negative thinking in relation to different types of hypothetical events. Results of a study investigating the CQ's association with depression and its capacity to detect residual cognitive vulnerability following an episode of depression are reported.

Adult↗

Cognitive therapy for major depressive disorder in primary care.

Cognitive therapy for depression is a psychological treatment designed to train patients to identify and correct the negative depressive thinking which, it has been hypothesised, contributes to the maintenance of depression. General practice patients meeting Research Diagnostic Criteria for primary major depressive disorder were randomly allocated either to continue with the treatment they would normally receive (which in the majority of cases included antidepressant medication) or to receive, in addition, sessions of cognitive therapy. At completion of treatment, patients receiving cognitive therapy were significantly less depressed than the comparison group, both on blind ratings of symptom severity made by psychiatric assessors and on a self-report measure of severity of depression. At three-month follow-up cognitive therapy patients no longer differed from patients receiving treatment-as-usual, but this was mainly as a result of continuing improvement in the comparison group.

Adult↗