Metabolism of testosterone in the anterior pituitary gland and the central nervous system of the European starling (Sturnus vulgaris)

The metabolism of testosterone was studied in vitro in anterior pituitary, hypothalamic and hyperstriatal tissues taken from male European starlings in the autumn. In all the tissues studied, testosterone was converted into 5alpha-androstan-17beta-ol-3-one (5alpha-DHT), 5beta-androstan-17beta-ol-3-one (5beta-DHT), 5beta-androstane-3alpha,17beta-diol (5beta-THT), 5beta-androstane-3,-17-dione and androst-4-ene-3,17-dione. The 5alpha-DHT was produced in significantly greater amounts by the pituitary gland than by the hypothalamus and hyperstriatum. The amount of 5alpha-DHT produced, however, was very low in comparison with the amounts of 5beta-reduced metabolites. The amount of 5beta-reductase was also higher in the pituitary gland than in the two nervous tissues. The ratios between the production of 5beta-DHT, 5beta-THT and 5beta-androstane-3,17-dione were, however, different in the three tissues: 5beta-DHT was produced in the greatest quantities by the hyperstriatum, while the production of 5beta-THT, 5beta-androstane-3,17-dione and androst-4-ene-3,17-dione was greatest in pituitary tissue. The role of 5alpha- and 5beta-reduced metabolites in the pituitary gland and in the brain of birds is unknown, but some possibilities arising from the present results are discussed.     

Seasonal changes in testosterone metabolism in the pituitary gland and central nervous system of the European starling (Sturnus vulgaris)

The metabolism of testosterone in the pituitary gland, the hypothalamus, and the hyperstriatum of the male European starling was studied in the breeding season (May) and at the beginning and the end of the photorefractory period (July and November). In the pituitary gland the percentage conversion of testosterone to androstenedione and to 5α-DHT did not show seasonal variation, while the conversion of testosterone to 5β-DHT and to 5β-3α-diol was increased two- to threefold when the birds became photorefractory (July and November). In the hypothalamus, the formation of the 5α-reduced metabolites did not show seasonal variation, while the formation of androstenedione was significantly greater in November than in July. In contrast, the formation of 5β-reduced metabolites in the hypothalamus was greater in May and July than in November. In the hyperstriatum, the formation of 5β-reduced metabolites was also greater in July and November than in May. These observations show that seasonal changes in the metabolism of testosterone in the pituitary gland and central nervous system of the starling are mainly characterized by changes in the formation of 5β-reduced metabolites and androstenedione.     

Sexual differences in the Japanese quail: behavior, morphology, and intracellular metabolism of testosterone

Three experiments were carried out to study whether differences in the intracellular metabolism of testosterone (T) can explain sexually differential responses to T in Japanese quail. In the first experiment, a series of dose-response curves in which length of Silastic testosterone implants was related to effects on several behavioral and physiological variables was established. In Experiment 2, adult males and females were assigned to six experimental groups: intact males and females (I-males and I-females), castrated males and females implanted subcutaneously with 40-mm Silastic implants of T (T-males and T-females), and castrated males and females without hormone treatment (CX-males and CX-females). No CX-bird (male or female) and no I-female exhibited male sexual behavior. However, I-males and T-males regularly copulated during the behavioral tests. No crowing was ever heard in CX-animals and I-females. T-females crowed less than T-males and their crowing sounded weaker than those of males. The cloacal glands of T-females were less developed than those of males. Radioimmunoassay of T and 5 alpha-DHT showed that T-males and T-females have similar plasma levels of androgens. No striking differences were observed in the way testosterone is metabolized by the pituitary gland and central nervous tissues of males and females. By contrast, the production of 5 alpha-dihydrotestosterone (5 alpha-DHT) and 5 alpha-androstane-3 alpha, 17 beta-diol (5 alpha, 3 alpha-diol) was higher in the cloacal glands of males than in those of females. These sex differences were not detected between T-males and T-females. In experiment 3, the cloacal gland of males produced more 5 alpha-reduced metabolites than those of females. The pituitary gland of females also produced more 5 beta-androstane-3 alpha, 17 beta-diol (5 beta, 3 alpha-diol). In syringeal muscles, the production of 5 beta-dihydrotestosterone (5 beta-DHT) and 5 beta, 3 alpha-diol was higher in females compared to males.     

Changes in aromatase activity in the neuroendocrine tissues of red grouse (Lagopus lagopus scoticus) in relation to the development of long-day refractoriness

Changes in aromatase activity in the neuroendocrine tissues of captive male and female red grouse (Lagopus lagopus scoticus) were measured during a photo-induced breeding cycle. The gonads enlarged and subsequently regressed, as a consequence of the development of long-day refractoriness, within 84 days of transferring photoinsensitive birds from a non-stimulatory to a stimulatory daylength. The object of the study was to determine whether long-day refractoriness is related to an increase in aromatase activity in the neuroendocrine tissues which might result in a greater inhibitory action of locally produced oestrogens on the release of LH-releasing hormone. Aromatase activity was measured and found to be present in the anterior pituitary gland, the anterior/preoptic hypothalamus, the posterior hypothalamus and the hyperstriatum dorsale. It was higher in the hypothalamus than in the hyperstriatum dorsale and higher in the posterior than in the anterior/preoptic hypothalamus. Aromatase activity in the posterior hypothalamus was higher in males than in females in short-day photosensitive and reproductively active birds, but not in long-day refractory birds. A similar sex difference was also observed in the anterior/preoptic hypothalamus in reproductively active birds. Hypothalamic aromatase activity in both sexes was directly related to gonadal function, being highest in reproductively active birds and lowest in long-day refractory birds. It is concluded that the development of long-day refractoriness is not related to an increase in aromatase activity in the neuroendocrine tissues. The decrease in aromatase activity in the neuroendocrine tissues in long-day refractory birds parallels a decrease in aggressive and territorial behaviour.     

The effects of castration and/or methimazole feeding on the pituitary response to temperature extremes by cockerels

The pituitary of goitrogen-treated White Leghorn cockerels is smaller in size than control birds and the pituitaries of castrated cockerels is nearly twice the size of control birds. The pituitary cells generated by these treatments may not be functional thyrotrophs or gonadotrophs and may not be able to respond to their usual stimuli. Low ambient temperature is a well-known stimulus to the thyroid gland acting through pituitary TSH. Cyclic-AMP-dependent protein kinase activity levels are used here as an index of cellular activity in the pituitary and thyroid glands. Castrated cockerels with or without methimazole treatment do not have an increased pituitary cAMP-dependent protein kinase activity in cold. Methimazole-treated birds have an exaggerated pituitary protein kinase response to cold stress when compared with controls. Pituitary cAMP-dependent protein kinase activity is paralleled by a similar activity increase in the thyroid gland of methimazole-treated cockerels and no increase in the thyroid of castrated birds. Castrated birds at all temperatures have an elevated thyroid cAMP-dependent protein kinase activity ratio which is interpreted as the result of removal of testosterone inhibition.     

Biochemical characterization and seasonal changes in the concentration of testosterone-metabolizing enzymes in the European great tit (Parus major) brain

Homogenates of diencephala obtained from brains of European great tits (Parus major) were incubated in the presence of tritiated testosterone (T) as precursor, and four metabolites produced from this steroid were formally identified and quantified. Conversion into 5 beta-dihydrotestosterone (5 beta-DHT) constituted the major metabolic pathway of T. Smaller amounts of 5 alpha-dihydrotestosterone (5 alpha-DHT), 5 beta-androstane-3 alpha, 17 beta-diol (5 beta-DIOL), and estradiol (E2) were also produced. The metabolism of T was time-dependent, and it varied as a function of the initial precursor concentration. The kinetics of 5 beta- and 5 alpha-reductases, as well as aromatase, followed the Michaelis-Menten model. It was found that 5 beta-reductase has a low apparent affinity for T, but is present in large concentrations. In contrast, the apparent affinity for T and the concentration of aromatase were approximately 3.9 times higher and 130 times smaller, respectively, than those of 5 beta-reductase. Intermediate values were found for 5 alpha-reductase. The validated assay was used to measure seasonal changes in the in vitro metabolism of T in the anterior (AH) and posterior (PH) hypothalamus and the cerebellum (CER) of free-living juvenile and adult male great tits. The production of 5 beta-DHT was low during the winter period in the PH of adult males, whereas the 5 beta-DIOL production was low in both parts of the hypothalamus at this time of the year. During autumn the production of these metabolites showed a transitory decrease in both parts of the hypothalamus of the juveniles. The production of 5 beta-reduced metabolites by the CER was high at all times of the year. In juveniles, the CER production of 5 beta-DHT did not change seasonally, whereas 5 beta-DIOL production peaked during summer. In the CER of adults, maximum production of both metabolites occurred during summer. Generally, less T was converted into 5 beta-reduced metabolites by the PH than by either the AH or the CER. E2 production was observed only in the AH and PH. With one exception (summer; AH), E2 production was high in both parts of the hypothalamus of adults throughout the year. In both AH and PH of juveniles, E2 production was low during summer. In these birds, it increased between summer and autumn in both parts of the hypothalamus, and also between autumn and winter in the PH. The production of 5 alpha-DHT did not change as a function of the season, the age of the birds, or the brain region.(ABSTRACT TRUNCATED AT 400 WORDS)     

Age-related changes in prolactin and growth hormone release from pituitary glands in vitro

The basal release of prolactin from cockerel anterior pituitary glands in vitro declined between 1 and 7 weeks of age, to a level less than that released by pituitary glands from 18 week old (adult) cockerels and hens. Basal growth hormone (GH) release increased between 1 and 7 weeks of age but had declined in adults to a level similar to that released from 4 weeks old cockerels. The responsiveness of the pituitary gland to hypothalamic stimulation, using hypothalami from 8 week old broiler fowl, was also age-related. Prolactin release was considerably higher from pituitaries of 1 week old cockerels compared to the other age groups. Stimulation of GH release by the hypothalamus was higher from pituitaries of both 1 and 7 week old cockerels compared to the other groups of birds. The increase in release of prolactin following incubation with thyrotrophin releasing hormone (TRH) declined between 1 and 7 weeks, but increased slightly in adult birds, whereas the increase in release of GH following TRH was higher from pituitaries of both 1 and 7 week old cockerels. Hypothalamic prolactin (Prl) releasing activity, measured as the ability of the hypothalamus to stimulate hormone release from 8 week old broiler fowl anterior pituitary glands, declined with the age of the donor cockerels. The hypothalami from adult hens secreted significantly more Prl releasing activity than did adult cockerel hypothalami. The secretion of GH releasing activity decreased markedly with the age of the donor bird. These results suggest that maturational patterns of hormone secretion in fowl are partly due to changes in autonomous hormone release, to changing patterns of hypothalamic activity and to differences in pituitary responsiveness to provocative stimuli.     

Regulatory effect of lithium on thyroxine metabolism in murine neural and anterior pituitary tissue

The conversion of T4 to T3 in the brain and anterior pituitary gland contributes significantly to the T3 content of these tissues and appears to be an important modulator of thyroid hormone action. In the present study, the antimanic agent lithium was demonstrated in cultured neural and pituitary tissue to have a significant inhibitory effect on the activity of low Km (type II) iodothyronine 5'-deiodinase (I5'D), the enzyme mediating T3 formation. At medium lithium concentrations of 3.3-5 mM, 15'D activity was decreased 44 +/- 3% (P less than 0.001) in the NB41A3 mouse neuroblastoma cell line and 48 +/- 2% (P less than 0.001) in the GH3 rat pituitary tumor cell line. This inhibitory effect was only observed in intact cells. Significant inhibition of this enzymatic process was also noted in the anterior pituitary gland of thyroidectomized rats injected 3-24 h earlier with either 4 or 10 mmol/kg BW LiCl. This decrease in low Km I5'D activity was accompanied by significant decreases in the serum T3 concentration and the pituitary nuclear T3 content. Renal high Km (type I) I5'D activity was unaffected by lithium administration. These studies demonstrate that lithium, an agent of proven therapeutic benefit in patients with manic-depressive illness, can affect changes in T4 metabolism and cellular T3 content in neural and anterior pituitary tissue. Given the prominent mood changes that occur in patients with disordered thyroid function, this finding suggests that the therapeutic benefits of lithium in affective illness may be derived in part from alterations in thyroid hormone economy in the brain.     

Thyroid hormone regulates rat pituitary insulin-like growth factor-I receptors

As we previously obtained evidence that insulin-like growth factor-I (IGF-I) inhibits T3-induced GH secretion and GH mRNA expression without affecting basal GH secretion in thyroidectomized rat pituitary cells grown in hypothyroid medium, we examined changes in IGF-I receptors in the pituitary gland, as induced by thyroid hormone. Thyroidectomized rats and a quantitative receptor autoradiographic method were used. The density of [125I]IGF-I-binding sites in the anterior pituitary gland decreased 4 weeks after thyroidectomy; that is a significant decrease in the number of the receptors compared to findings in control rats (P less than 0.01). The affinity (Kd) remained unchanged. There were no changes in binding parameters in the ventroposterior thalamic nucleus in the brain, renal cortex, and liver parenchyma. The ip administration of T4 once a day (48 micrograms/kg) for 1-2 weeks compensated for the decrease in the binding capacity of [125I]IGF-I-binding sites to that of the control values (P less than 0.01). We propose that IGF-I receptors in the anterior pituitary gland may be regulated by thyroid hormone.     

Correlation between LH secretion in castrated rats with cellular proliferation and synthesis of DNA in the anterior pituitary gland

Testosterone metabolism in the brain and pituitary and cloacal glands of male and female Japanese quail was studied in vitro during sexual maturation (from 1 day to 5 weeks after hatching). The production of 5 alpha-dihydrotestosterone in the hyperstriatum and cloacal gland and that of androstenedione in the cloacal gland of males was highest at 1 day after hatching, which could be related to the peak of plasma androgens previously demonstrated in neonatal quail. 5 beta-Reductase activity was very high in the brain, but not the pituitary or cloacal glands of young chicks and decreased markedly, especially in the hypothalamus, during sexual maturation. As 5 beta-reduced metabolites of testosterone are inactive androgens, it is suggested that the decrease of 5 beta-reductase activity with age corresponds to a potentiation of the effects of testosterone at the level of the brain.     

Photoperiodic control of testosterone metabolism, plasma gonadotrophins, cloacal gland growth, and reproductive behavior in the Japanese quail.

The changes in plasma gonadotrophins and testosterone, in cloacal gland area, and in reproductive behavior were observed in male Japanese quails after transfer to long days or testosterone implantation and were correlated with the testosterone metabolism in the hyperstriatum, hypothalamus, pituitary, and cloacal gland. Long days stimulate the growth of the cloacal gland and at the same time enhance its production of androstenedione from testosterone. This increased 17β-hydroxysteroid dehydrogenase activity is correlated at the individual level with cloacal gland area but not with plasma testosterone. Similarly the changes observed in some reproductive activities (aggressive behavior and struts) are correlated with individual differences in the brain metabolism of testosterone (hyperstriatal or hypothalamic production of androstenedione), but not with plasma testosterone. The plasma luteinizing hormone is also related to testosterone metabolism rather than to the circulating level of the hormone (negative correlation with the production of 5α-dihydrotestosterone in the pituitary). The testosterone metabolism in target organs thus appears of critical importance in the control of reproduction and seems largely responsible for the occurrence of individual differences. After exposure to 12 long days the mean testosterone metabolism in the pituitary is also strongly affected (increased 5β-reduction) though not in the same way as after 2 months of photostimulation. It is suggested that these metabolic changes at the pituitary level may play some role in the induction of the increased responsiveness to luteinizing hormone-releasing hormone which can be observed in quails after exposure to 7 long days.     

Effects of in vivo corticosterone treatment on the in vitro metabolism of testosterone in the comb and brain of the young male chicken

Male chickens kept in constant light were injected from their second to their 12th day of life daily either with 2.5 mg of corticosterone or with a control solution. In both groups of birds, the in vivo metabolism of labeled testosterone by the comb and by brain tissues (hyperstriatum, hypothalamus, pituitary gland) was then studied.The experimental treatment blocked the growth of the comb observed in control birds. In this tissue, it also reduced the production from testosterone of 5α-dihydrotestosterone and of 5α-androstane-3α,17β-diol, but it increased the production of 5β-androstane-3α,17β-diol. These modifications did not appear in any brain tissue; they were not accompanied by changes either of LH or of testosterone circulating levels or of the testes' weights.     

Modulation of thyroid hormone nuclear receptor levels by L-triiodothyronine (T3) in the rat pituitary

The concentration of thyroid hormone nuclear receptors varies from one tissue to another, the anterior pituitary (AP) gland possessing the highest. Since 3,5,3',1-triiodothyronine (T3) controls within a narrow range the secretion of TSH from the pituitary gland, this study was carried out to establish whether T3 modulates its own pituitary nuclear receptors and if so, whether this modulation is correlated with the thyroidal status and TSH secretion. Salt-solubilized T3 nuclear receptors were measured in the AP gland of thyroidectomized and intact adult male rats as well as in thyroidectomized rats treated with T3. In intact male rats the maximum binding capacity of pituitary T3 nuclear receptors (MBC-T3nR), determined by Scatchard analysis, was 578 +/- 45 fmoles T3/mg protein or 27 +/- 3 fmoles T3/AP (mean +/- SEM, n = 19). 2 weeks after thyroidectomy there was a marked decrease in serum T3 and T4 concentrations as well as in the MBC-T3nR (231 +/- 26 fmoles T3/mg protein or 9.3 +/- 1.2 fmoles T3/AP, n = 7) which was still observed 8 and 16 weeks after thyroidectomy. The affinity constant (Ka) of T3 for its pituitary nuclear receptors was significantly greater in thyroidectomized rats than in intact rats (3.61 +/- 0.70 vs. 1.09 +/- 0.15 X 10(10) M-1, P less than 0.001). To test whether treatment with T3 would restore a normal MBC-T3nR, 2-week thyroidectomized rats were injected with T3(0.5 micrograms/100 g b.w.) and killed 10 min, 1, 3, 15 or 24 h after T3 injection. 10 min after T3 injection MBC-T3nR was not altered but it returned to normal values 1 h after injection (441 +/- 97 fmoles T3/mg protein) and was maintained so for at least 3 h. 15 h after T3 injection MBC-T3nR was again decreased in spite of serum T3 levels that were twice as high as in normal rats. In contrast, when T3 was injected at the dose of 1.0 micrograms/100 g b.w. the MBC-T3nR was maintained within the normal range as long as 24 h after the injection (428 +/- 125 fmoles T3/mg protein) with serum T3 concentrations that were twice the normal levels (1.27 +/- 0.06 vs. 0.67 +/- 0.01 ng/ml). These results support the hypothesis that T3 modulates the concentration of its own nuclear receptors in the rat pituitary gland. The absence of any effect of T3 10 min after injection is suggestive of an effect of T3 on the synthesis of its receptors rather than on an alteration of unoccupied receptors that would require T3 for adequate configuration and detection. This modulation of pituitary T3 receptors by T3 may provide an additional mechanism of regulation of TSH secretion in thyroid insufficiency.     

Adrenocortical responses to novel stressors in acutely or repeatedly starved chickens

The effect of starvation on the corticosterone responses of immature cockerels to acute, novel stress has been determined. The marked corticosterone responses of fed birds to either horizontal treadmill exercise (0.04 km/hr) or intravenous adrenocorticotrophic hormone (ACTH) administration (P less than 0.001 in both cases) were reduced by starvation (P less than 0.01 and P less than 0.001, respectively). This reduction did not appear to be due to either feedback inhibition of corticosterone on the hypothalamus or pituitary, or to reduced adrenal responsiveness to endogenous ACTH. Starvation significantly elevated the basal level of circulating corticosterone (P less than 0.001), but the magnitude of this elevation and the level of corticosterone attained were less (P less than 0.05) in birds that were accustomed to starvation. This habituation of adrenocortical activity may be due to reduced pituitary ACTH secretion, and was specific in that the corticosterone responses to novel stressors were unaffected.     

Thyroid-pituitary function in eight anencephalic infants

The function of the thyroid pituitary axis was investigated in 8 anencephalic infants with no hypothalamus. Thyrotrophin (TSH), thyroxine (T4), 3,5,3'-triiodothyronine (T3) and 3,3',5'-triiodothyrone (reverse T3 and rT3) were measured in the cord blood in 5 cases and during the first 4 h of life in 3 cases. TSH response to synthetic thyrotrophin-releasing hormone (TRH) (200 microgram iv) was carried out in two cases and thyroid hormone response to bovine TSH (5 IU iv) was evaluated in 3 cases. The following results wre obtained: 1) The pituitary gland was found in all infants and the thyroid was normal both grossly and by microscopic sections. 2) TSH levels at birth were normal but there was no spontaneous post-delivery surge. 3) T4 and T3 values at delivery were within normal range, but no T3 increase was present after birth. rT3 levels at birth were higher than normal in 3 cases. 4) Administration of TRH caused a marked and rapid TSH release. 5) Thyroid hormone response to TSH was normal. The present findings suggest that in the anencephalic foetus both pituitary TSH-secreting cells and the thyroid gland do develop despite the absence of the hypothalamus and are able to function if adequately stimulated.     

Growth hormone in encephalectomized rat fetuses, with comments on the effects of anesthetics.

Plasma and pituitary immunoreactive growth hormone (GH) was measured in 21.5-day-old rat fetuses under various experimental conditions. Encephalectomy on day 19.5 was used as a method for depriving the fetus of its hypothalamus. The fetuses were recovered on day 21.5 under maternal pentobarbital anesthesia. Total encephalectomy or partial encephalectomy (ablation of superficial brain structures) similarly affected fetal growth. The mean GH contents of the pituitaries were not significantly different in the four groups of fetuses studied: controls from intact females (1.38 +/- 0.19 mug/gland), controls from females submitted to surgery on day 19 (1.47 +/- 0.13 mug/gland), surgically encephalectomized fetuses (1.13 +/- 0.12 mug/gland), sham-operated fetuses (1.19 +/- 0.10 mug/gland). The mean plasma GH levels were the same in control fetuses of intact females (147 +/- 8 ng/ml) and in control fetuses of females submitted to surgery (168 +/- 9 ng/ml). The values were lower in sham-operated fetuses (118 +/- 11 ng/ml) and considerably reduced (P less than 0.001) in encephalectomized fetuses (60 +/- 8 ng/ml). Plasma GH was higher in the fetuses of females killed less than 2 min earlier, than in the fetuses of anesthetized females. In dams anesthetized with pentobarbital or ether, the fetal plasma levels of GH were not different after 15 or 45 min of maternal anesthesia. Under maternal urethane anesthesia, the fetal plasma GH was at 15 min significantly lower than it was under (P less than 0.01) or pentobarbital (P less than 0.05); 30 min later, it had increased by 40% (P less than 0.025). It appears that the release of GH in the fetus can be modified by anesthetics, and that some GH still is released by the pituitary gland in the absence of the hypothalamus.     

Hypothyroidism increases substance P concentrations in the heterotopic anterior pituitary

The regulatory effects of thyroid hormone on adenohypophysial substance P (SP) were studied in heterotopically implanted anterior pituitaries. Three or four anterior pituitaries from 21-day-old rat pups were implanted under the renal capsule in 175- to 200-g adult rats. The donor and recipient animals were sex matched. One week after implantation, animals were thyroidectomized or sham operated. A separate group of animals received daily T4 treatment (1.5 g/100 g, ip). After 2 weeks, the native and heterotopic pituitaries were assayed for SP, TSH, PRL, and LH. Thyroidectomy resulted in a 3- to 10-fold increase in the SP concentration in both the heterotopic and native pituitaries compared to euthyroid values. T4 treatment suppressed the SP levels in the heterotopic pituitaries of the thyroidectomized rats. In contrast to the reduction of TSH concentrations in native pituitaries in thyroidectomized animals vs. controls, TSH concentrations in the heterotopic pituitaries of thyroidectomized rats were approximately 10 times greater than those in euthyroid animals. PRL concentrations were unaffected by hypothyroidism in native and heterotopic pituitaries. Thyroidectomy resulted in a decrease in LH concentrations in the native anterior pituitary, without affecting LH concentrations in the implanted pituitary. These findings indicate that a direct link from the hypothalamus to the anterior pituitary is not required for the pituitary SP response to hypothyroidism.     

Glucose tolerance and pancreatic hormones in thyroidectomized and thyroid hormone-injected cockerels

The effect of surgical thyroidectomy and of T4/T3 injections on basal and glucose-induced concentrations of plasma insulin and glucagon has been investigated in 20-week-old domestic chickens. Birds injected daily (im) for 2 weeks with T4/T3 (50 micrograms/day) had marginally lower fasting glucose concentrations whereas thyroidectomy had no effect. Glucose tolerance to an intravenous injection of glucose (0.5 g/kg) was impaired in T4/T3 injected animals although the peak hyperglycemia was identical with sham-operated animals. This was associated with significantly reduced basal and glucose-induced insulin concentrations. However, fasting plasma glucagon concentrations were significantly elevated in this group as was the magnitude of the glucose-induced suppression of glucagon release 10 min after injection (48% decline vs 34% in sham-operated animals). Basal concentrations of plasma insulin were markedly elevated in thyroidectomized animals and were associated with only mildly depressed plasma glucagon levels. The absolute concentrations of plasma insulin remained higher in the thyroidectomized birds as compared with those of sham-operated or T4/T3 injected animals after the glucose challenge, although within 30 min after glucose injection they had significantly declined below preinjection levels. This was associated both with significantly reduced plasma glucose concentrations 30 min after injection and the lowest absolute levels of plasma glucagon. The rebound in plasma glucagon in sham-operated animals in response to the rapid decline in glucose concentrations was not as pronounced in either thyroidectomized or T4/T3 injected animals. In conclusion these studies illustrate the secretory dynamics of avian pancreatic endocrine islets in response to both absolute glucose levels and glucose requirements as affected by the thyroid state of the bird.     

Studies on the feedback regulation of gonadotropin concentrations in male rats. (II). Partial characterization of 5 alpha-reductase in the medial basal hypothalamus and anterior pituitary gland

To evaluate the testosterone (T) 5 alpha-reductase activity in medial basal hypothalamus (MBH) and anterior pituitary gland of the adult male rat, whole homogenate of MBH or anterior pituitary glands was incubated with 14C-T in the presence of coenzymes under various experimental conditions. Major metabolites were 5 alpha-dihydrotestosterone (DHT), 5 alpha-androstane-3 alpha (beta), 17 beta-diol(3 alpha(beta)-diol) and delta 4 androstenedione. The activity of 5 alpha-reductase was expressed as the sum of the amount of DHT and 3 alpha(beta)-diol formed after incubation. The metabolites converted from T was separated and identified by thin layer chromatography and confirmed by recrystallization. The anterior pituitary gland possessed about four times higher 5 alpha-reductase activity compared with that in MBH. NADPH was essential for 5 alpha-reductase activity. They existed in microsomal fraction. They had same optimum temperature and almost same optimum pH. The Michaelis constant of the 5 alpha-reductase for T in MBH and anterior pituitary gland was 3.1 X 10(-7) M and 5.6 X 10(-7) M, respectively. These results suggest that 5 alpha-reduced metabolites of T, especially DHT have some physiologically significant roles in not only MBH but also anterior pituitary gland. Furthermore, it is noteworthy that 5 alpha-reductase in the anterior pituitary showed higher activity than that in MBH.