Anterior Hypophysis Research Articles

Pars intermedia of the hypophysis of rats after early-postnatal lesions of the basal hypothalamus: quantitative and qualitative observations.

Lesions were made by electrical coagulation in the base of the hypothalamus of rats, 20 to 24 h after birth. Subsequent growth of the hypophysis was examined volumetrically and histologically on the 40th and 60th days after the operation, paying special attention to the pars intermedia. Growth retardation of the hypophysis was noticeable after 60 days in rats with lesions of the hypophysial stalk (groups 1 and 2) and the posterior portion of the median eminence (group 4), especially in animals in which the stalk was completely (group 1) or almost completely (group 2) transected. Notwithstanding the growth retardation of the hypophysis, the ratios of the volume of the pars anterior to that of the whole hypophysis in groups 1 and 2 were not significantly different from those in group 3 (animals with a lesion of the anterior portion of the median eminence), groups 4 and 5 (animals with a lesion in the hypothalamus elsewhere than the stalk and median eminence), and normal controls of the same age (group 6). In contrast to this, the ratio of the volume of the pars nervosa to the total gland in group 3, and more especially in groups 1 and 2, had considerably diminished, and that of the pars intermedia in groups 1 and 2 had markedly increased, after 60 days in comparison with those in groups 3, 4, 5, and 6. These results indicate that the pars intermedia of animals in groups 1 and 2 was hypertrophic compared with the pars anterior and pars nervosa. These volumetric data seem to correspond with the finding that neurosecretory material was not present in the pars nervosa in groups 1 and 2, but was abundant in groups 3, 4, 5, and 6. After 60 days, the pars intermedia of group 1 consisted chiefly of well-developed cells, as in normal adult rats. On electron microscopic examination, however, they were found to differ from normal mature cells in the following three points: (1) most of the secretory granules were vesicular with little or no opacity; (2) the endoplasmic reticulum frequently showed cisternae; (3) nerve terminals were not encountered at the surface of the glandular cells. The former two points suggest that these cells are functionally active, an observation that agrees with the results of volumetric findings. It is concluded from these data that, in the absence of hypothalamic control, the pars intermedia of the hypophysis in rats grows actively after birth, while the anterior hypophysis seems to be inactive and atrophic [unpublished].

Testosterone “receptors” in purified nuclei of rat anterior hypophysis

In this work, the presence of two macromolecular associations of [ 3H]-testosterone in purified nuclei of rat anterior hypophysis was demonstrated. After incubation of slices of hypophyseal tissue with [ 3H]-testosterone purified nuclei were obtained free from cytoplasmic contamination. After extraction with M NaCl and gel filtration on Sephadex G 200, two peaks of bound radioactivity were obtained. The first, with a concentration of 0·6 × 10 −13 mol by mg of proteins is excluded from gel Sephadex G 200, the second with a concentration of 2·1 × 10 −13 mol by mg proteins is retained on this gel. There is no binding with histones. The radioactive material bound to the nuclear “receptors” is mainly testosterone. The amount of dihydrotestosterone is small. Again, we have noted the presence of a non polar steroid. They represent respectively 66,7 and 7% of the radioactivity of the chromatogram.

Effects of gonadotropins on the occurrence of permanent changes in the testis of mice given neonatal estrogen injections.

Daily injections of gonadotropins (PMS, HCG or PMS-HCG) for 15 days from the day of birth, 1 I.U. for the first 10 days and 2 I.U. for the following 5 days, resulted in a hypertrophy of interstitial cells in the testes of mice at 15 days of age. The seminal vesicles were highly stimulated by endogenous androgen in these animals. In the testes of the 60-day-old males which had been given daily injections of estradiol-17β(E) for 15 postnatal days, 20μg for the first 10 days and 40μg for the next 5 days, spermatogenesis was arrested or the seminiferous epithelium was severely damaged. In contrast, the testes of those receiving neonatal injections of E and PMS, E and HCG, and E and PMS-HCG were undergoing active spermatogenesis, showing no damages to the seminiferous epithelium. These findings appear to indicate that neonatally injected estrogen is antagonized by androgen secreted from the testes in response to exogenous gonadotropins and, as a consequence, that the gonadotropin secretion from the anterior hypophysis is not affected.

Oestrogen uptake by the central nervous system.

This presentation covers three areas in relation with the mechanism of oestrogen action on the central nervous system. The ability of the uterus, vagina, anterior pituitary and anterior hypophysis to take up and retain oestradiol has been proposed as a distinctive character for the oestrogenic target organs. Although no specific protein receptors have been isolated in the neocortex, the administration of oestradiol was able to increase the incorporation of cytidine to RNA, and the protein synthesis. Those findings, together with the fact that oestradiol is concentrated and retained in the nuclei of the cerebral cortex, forced us to review the concept of target organs. The presence of very small quantities of oestradiol in the central nervous system cell nuclei may reflect the amounts that the tissue requires, and the emphasis that has always been put on quantity should be placed on there-sholds for oestrogen action in different tissues. The capacity of progestagens to compete with oestradiol binding was evaluated by organotypic culture of the hypothalamus. In a group of experiments, progestagens were added before oestradiol and, in the other group, both progestagens and oestradiol were added simultaneously to the medium. Oestradiol binding was significantly inhibited when either of the progestagens derived from 17Α-hydroxyprogesterone (chlormadinone acetate (CA) and medroxyprogesterone acetate (MPA) was added simultaneously. When added previously to oestradiol, progestagens behaved differently. MPA diminished the oestradiol binding significantly; CA, on the contrary, increased it. RO4–8347, a compound derived from retroprogesterone, diminished the oestradiol binding when added previously, but not when added simultaneously. Lynestrenol and norgestrel, both 19-norsteroids, inhibited the oestradiol binding when added simultaneously, but not when added previously. Catecholamines and oestrogens participate in the control of ovulation and it was thought worthwhile to investigate their relationships in the hypothalamus and the uterus. The simultaneous administration of epinephrine and labelled 17Β-oestradiol injected i.p. produced a significant increase in the uptake of oestradiol by the anterior hypothalamus and a diminution in the uterus. When norepinephrine and 17Β-oestradiol were simultaneously injected, the uptake of oestradiol was increased in the uterus and not modified in the hypothalamus. As the concentration of histamine is higher in the hypothalamus than in any brain region, it seemed interesting to us to study the effect of histamine on the uptake of oestradiol and testosterone. Histamine increased the uptake of labelled oestradiol by the uterus and the hypothalamus. When histamine effects were studied in relation with testosterone uptake, it increased the hypothalamic, but not the uterine uptake. Even knowing that the mammalian pineal gland has an inhibitory effect on gonadal function, little attention has been paid to the role of gonadal hormones on pineal activity. In view of the contradictory results concerning the action of oestradiol on the pineal gland, we have studied in our laboratory the uptake of labelled oestradiol by this gland and the hydroxyindole-O-methyl transferase (HIOMT) modifications produced by oestradiol and/or norepinephrine administration. Our results demonstrate that the pineal ability to take up oestradiol was significantly higher than that of the uterus. Besides, the administration of oestradiol to spayed female rats inhibited the pineal HIOMT activity, this effect being reversed by norepinephrine, which when injected alone modifies neither the uptake of oestradiol nor HIOMT activity.

THE BINDING OF 3H-OESTRADIOL TO MACROMOLECULES OF ANTERIOR PITUITARY TISSUE IN RATS

3H-oestradiol has been found to be concentrater preferentially and retained in the anterior hypophysis of male and female rats. Moreover, the binding sites appear to be highly specific and limited in number. Furthermore, nearly all the radioactive material has been found to be chemically unchanged oestradiol.

Ataxia telangiectasia and growth failure.

Ataxia telangiectasia is a familial disorder characterized by ataxia, telangiectasia, and recurrent sinopulmonary infections. 1-3 Retardation of growth is a common feature. Many patients have, in addition, immunologic deficiencies 4 and some have endocrine disturbance. Sexual infantilism, absence of ovaries, bilateral dysgerminomata, hypoplastic adrenals, unspecified cytomegalic changes of the anterior hypophysis, and an unusual form of diabetes mellitus are among the endocrine disturbances reported. 3,5-7 The present study was undertaken to extend previous endocrine observations, to evaluate growth hormone release, and to determine if any measurable endocrine disturbances could be responsible for the growth retardation. Report of Cases Case1 and Case 2.—A boy 4 years, 10 months of age (case 1) and his 6-year-old sister (case 2) had all the typical findings of advanced ataxia telangiectasia (Table 1). Telangiectasis of the eyes, face, head, neck, and trunk; cafe au lait markings, truncal ataxia, and deficiency in fine motor coordination

Etude du récepteur cytoplasmique de la (1,2- 3H) testosterone dans l'hypophyse antérieure et l'hypothalamus du rat

The anterior pituitary and the hypothalamus of the normal and castrated rat contain soluble receptors for testosterone, present in the 105.000 g supernatants. The capacity of macro-molecular fixation of testosterone is greater in anterior hypophysis than in hypothalamus. Raising the incubation temperature of slices and of homogenates results in a decrease of the binding capacity of testosterone. These receptors are macromolecules whose molecular weight most likely exceeds 100.000 and whose nature is, at least in part, protein. The bound radioactive material consists partly of testosterone and partly of an unidentified steroïd (Compound X). Dihydrotestosterone and 4-androstene-3,17-dione are minor constituents.

In vitro uptake of tritiated oestradiol by the anterior hypothalamus and hypophysis of the rat.

ABSTRACT The anterior, middle, and posterior hypothalamus, the cortex cerebri, the anterior hypophysis as well as the diaphragm of adult ovariectomized rats were incubated in vitro with tritiated 17β-oestradiol. The uptake of tritiated oestradiol was differentially distributed intracerebrally with higher accumulation in the anterior hypothalamus and the hypophysis. Lowering the temperature of the incubation medium caused a reduction in the uptake of radioactivity by the anterior hypothalamus as compared to that found in other brain tissues. Tritiated oestradiol taken up in vitro by the anterior hypothalamus and the hypophysis tended to be retained after further incubation in a steroid-free medium. The addition of non-radioactive 17β-oestradiol to the medium inhibited the uptake of tritiated oestradiol by these tissues. Moreover, pretreatment with non-radioactive 17β-oestradiol in vivo prevented the preferential accumulation of tritiated oestradiol in vitro in the anterior hypothalamus and the hypophysis. These results indicate that oestradiol is preferentially taken up in vitro by the anterior hypothalamus and the hypophysis of the rat.

In vitro uptake of tritiated oestradiol by the rat anterior hypothalamus during the oestrous cycle.

ABSTRACT The anterior, middle and posterior hypothalamus, the cortex cerebri, the anterior hypophysis, and the diaphragm of postpubertal rats at different phases of the oestrous cycle were incubated in vitro with tritiated 17β-oestradiol. Uptake of radioactivity by the anterior hypothalamus at prooestrus and oestrus was lower than that at dioestrus. In contrast no fluctuation in the concentration of the radioactivity in the other parts of brain, the hypophysis and muscle was observed during the oestrous cycle. These in vitro findings are consistent with the in vivo observations of cyclic changes in phase with the oestrous cycle of the amount of radioactive oestradiol taken up by the anterior hypothalamus following the injection of tritiated oestradiol (Kato et al. 1969b). Thus it is further suggested that the oestradiol receptor in the anterior hypothalamus of the rat is involved in the physiological regulation and maintenance of cyclic changes in the hypothalamo-pituitary system through the mechanism of action of feedback of oestrogen.

Hypothalamic-hypophysial adrenal and thyroid systems: observations in fetal rats subjected to hypothalamic destruction, brain compression and hypervitaminosis A.

AbstractRegulation by fetal hypothalamus of adrenocorticotrophic and thyrotrophic function of the fetal anterior hypophysis in the rat was studied by: (1) destruction of the fetal hypothalamic area with an electrocoagulator, (2) compression of the fetal brain by injected paraffin into the fetal skull and (3) induction of fetal exencephaly by hypervitaminosis A in the mother.The body weight of fetuses in which the hypothalamus was damaged was significantly less than that of littermate controls. Volume of the anterior hypophysis was small in fetuses injected with paraffin. The anterior hypophyses were present in all exencephalies, and showed abnormal forms but no reduction in volume. The adrenals were very small in all fetuses in which the hypothalamus was damaged, accompanied by conspicuous shrinkage of cortical cells, while the thyroids were not changed in volume. The height of the follicular cells decreased slightly.The observations suggest that in the late period of fetal life in rats, the hypophysial‐adrenal system is regulated largely by the hypothalamus, but that the hypophysial‐thyroid system is not fully under the control of the hypothalamus.

An attempt to separate a sheep pineal extract fraction showing antigonadotropic activity.

The fraction F3 obtained after gelfiltration of a pineal extract on Sephadex G-25 (Fine) which inhibitsin vitro the secretion of FSH of the anterior hypophysis has been chromatographed on the weak cation-exchanger Amberlite IRC-50, XE-64. This method which was very useful as a purification step of the Sephadex G-25 fraction F2 and has been used with success to isolate the peptide hormones of the neurohypophysis, does appear to be unsuitable for further purification of a pineal fraction with inhibiting activity.

The uptake of 3H-oestradiol by the anterior hypophysis and hypothalamus of male and female rats.

The anterior hypophysis and hypothalamus of male and female rats given 3H-oestradiol were examined with regard to 1) the kinetics of the uptake of the radioactive material, 2) the chemical nature of the labelled material, and 3) the influence of non-labelled oestradiol-17β, oestradiol-17α and testosterone on the uptake of 3H-oestradiol. The anterior hypophysis was found to concentrate and retain oestradiol in basically the same manner in male and female rats. The pattern of the uptake was similar to that of the uterus and vagina, with a concentration peak 2 hours after the injection. Non-target tissues such as cerebral cortex, liver and blood attained their maximum uptake already 15 minutes after the injection. Thereafter the concentration gradually decreased. The ratio between the concentration of labelled material in the anterior hypophysis and brain cortex gradually increased until a peak was reached at 8 hours in both sexes. In the female, the concentration of labelled material in the anterior hypophysis was then 106.3 times greater than in the brain cortex, while in the male the ratio was 63.2. In the hypothalamus the uptake followed a pattern similar to that of the brain cortex. However, in the former the concentration of labelled material was consistently greater than in the latter. At maximum uptake, registered 4 hours after the injection, the concentration was about two times greater in the hypothalamus than in the cerebral cortex. The neurohypophysis contained, on an average, 1/6 of the amount of radioactive material registered in the anterior lobe one hour after the injection, but it was about two times greater than in the brain cortex. Isolation and identification of the radioactive material in the anterior hypophysis and hypothalamus showed that in both sexes nearly all of it was chemically unchanged oestradiol. Graded doses of non-labelled oestradiol-17β were found to decrease the uptake of 3H-oestradiol in the anterior hypophysis and hypothalamus almost linearly, while the concentration of labelled material in the brain was unaltered. Oestradiol-17α and testosterone were without significant effect on both the pituitary and hypothalamic accumulation of 3H-oestradiol. Therefore, a limited number of binding sites, with a high degree of specificity for oestradiol, appear to exist in both tissues. The results were essentially the same in male and female rats.

Changes in the lipid composition of anterior hypophysis, blood plasma and liver. II. Histological changes in the anterior hypophysis; in the foetus and its dam in the bovine.

Summary. Total lipid, total phospholipid and total fatty acid patterns of the anterior hypophysis, blood plasma and liver of foetuses and their dams at 4- and 8-month gestation intervals were determined. Differences in total lipid and total phospholipid between foetuses of different ages and their dams were not significant, and the differences in total fatty acid pattern among the foetuses and among the dams were minor at either time. Differences were significant in the total fatty acid patterns between the foetuses and their dams. The differences were mostly in the concentrations of the linoleic acid (C 18:2ω6), linolenic acid (C 18:3ω3) and oleic acid (C 18:1ω9) families of fatty acids. The concentration of linoleic acid in various tissues of the dam was significantly higher than in the foetus, but arachidonic acid (C 20:4ω6, a major metabolite of linoleic acid) was significantly lower in the plasma and liver of the dam than in the foetus; in the anterior hypophysis the differences were not significant. Linolenic acid (C 18:3ω3) was either absent or present in trace amounts (<0·1%) in the foetal tissues; in the dam it was present in significant amounts (1·5 to 5%). In the dams, oleic acid concentration was significantly lower than in the foetus in the plasma and anterior hypophysis and somewhat higher in the liver. Microscopic examination of the anterior hypophysis of the foetus showed mainly undifferentiated chromophobes with a few sparsely granulated acidophil cells; in the dam, the gland was composed mainly of clumps of acidophils and a few chromophobes.

Recent Advances in the Biochemistry of Thyroid Regulation

Publisher Summary This chapter examines various aspects of thyroid regulatory processes and discusses thyrocalcitonin. In context to thyroid hormone regulation, thyrotropin-releasing factor (TRF) is produced in the hypothalamus and arrives at the pituitary via the hypophyseal portal blood system. TRF mediates the release of thyrotropin from the anterior hypophysis. The thyrotropin release is inhibited by thyroxine, presumably free thyroxine, and the inhibition is dose dependent. The excessive levels of thyroxine depress thyrotropin release and lower thyroxine levels that result in increased thyrotropin release from the anterior pituitary. Thyroid-stimulating hormone (TSH) essentially stimulates thyroid hormone synthesis and secretion by the thyroid gland. Thyroxine and tri-iodothyronine are bound to specific binding proteins in the blood. The amounts and binding constants of the specific thyroid-binding proteins, together with the rate of thyroid hormone release from the thyroid, determine the amount of free thyroxine in the blood. Free thyroxine levels are determined not only by the rate of hormone release from the gland but also by the rate of removal of free thyroxine from the blood compartment by binding proteins and processes in tissues.

Multiplication of Avian Leukosis Virus in Endocrine Organs of Congenitally Infected Chickens&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;

Thyroid, parathyroid, pituitary, and adrenal glands from viremic chickens congenitally infected with avian leukosis virus (ALV) were examined with the electron microscope to ascertain whether the epithelial cells supported multiplication of ALV. Virus multiplied in parenchymal cells of the anterior hypophysis, thyroid, parathyroid, and adrenal cortex. No viral buds were found associated with parenchymal cells of the adrenal medulla.

Effect of clomiphene on the uptake of estradiol by the anterior hypothalamus and hypophysis.

The administration of clomiphene caused a marked depression in the uptake of tritiated estradiol by the anterior hypophysis and a smaller depression of estrogen uptake by the anterior hypothalamus in adult ovariectomized rats. The minimal effective doses were 0.1 mg/kg/day for 4 days or 1 mg/kg in a single injection. The degree of depression was a function of the dose in both cases. In contrast, clomiphene was without effect on the uptake of estradiol by the posterior hypophysis, the cerebrum, the cerebellum, or the middle and posterior hypothalamus. These results suggest that clomiphene binds or occupies the estradiol-binding “receptors” in the anterior hypophysis and the anterior hypothalamus. (Endocrinology82: 1049, 1968)

FACTORS AFFECTING UPTAKE OF ESTRADIOL-6,7-3H BY THE HYPOPHYSIS AND HYPOTHALAMUS

The uptake of labeled estradiol by the anterior hypothalamus and the anterior hypophysis was depressed by the concomitant injection of 1.8 or 4 μg of unlabeled estradiol. In contrast, the treatment had little or no effect on the uptake of estradiol in the cerebral cortex and cerebellum. The labeled estradiol taken up initially by the hypothalamus and hypophysis was not removed by the subsequent injection of unlabeledunlabeled steroid. In contrast to 17β-estradiol, pretreatment with 17α-estradiol, even in large amounts, did not alter the uptake of 17β-estradiol by the anterior hypothalamus and hypophysis. These results provide further evidence for specific estradiol-binding receptors of limited capacity in the anterior hypothalamus and anterior hypophysis. (Endocrinology 80:1133,1967)

PREFERENTIAL UPTAKE OF ESTRADIOL BY THE ANTERIOR HYPOTHALAMUS OF THE RAT

Adult ovariectomized rats were injected with a small dose of tritium-labeled estradiol and the uptake and retention of radioactivity in various parts of the brain were measured. The anterior hypothalamus and median eminence showed a characteristic pattern of uptake and retention of radioactivity similar to that shown by the uterus and vagina. The radioactivity taken up was extracted and shown to be largely estradiol itself. Other parts of the brain, which did not selectively take up and retain radioactivity, either converted a relatively larger fraction of the estradiol to estrone and other products or took up estrone made elsewhere in the body from the injected estradiol. The anterior hypophysis was also shown in these experiments to take up and retain estradiol and to convert only a small fraction of it to estrone. The selective uptake and retention of estradiol by the anterior hypothalamus and median eminence suggests a means by which the hormone could initiate the sequence of reactions by which it exe...

Factors affecting uptake of estradiol-6,7-3H by the hypophysis and hypothalamus.

The uptake of labeled estradiol by the anterior hypothalamus and the anterior hypophysis was depressed by the concomitant injection of 1.8 or 4 μg of unlabeled estradiol. In contrast, the treatment had little or no effect on the uptake of estradiol in the cerebral cortex and cerebellum. The labeled estradiol taken up initially by the hypothalamus and hypophysis was not removed by the subsequent injection of unlabeledunlabeled steroid. In contrast to 17β-estradiol, pretreatment with 17α-estradiol, even in large amounts, did not alter the uptake of 17β-estradiol by the anterior hypothalamus and hypophysis. These results provide further evidence for specific estradiol-binding receptors of limited capacity in the anterior hypothalamus and anterior hypophysis. (Endocrinology 80:1133,1967)

Essential Fatty Acid Deficiency and Its Effects upon Reproductive Organs of Male Rabbits

To study the effects of essential fatty acid deficiency upon rabbits, especially upon spermatogenesis, five immature, male, New Zealand rabbits were fed a purified diet devoid of fat for 14 weeks. The fatty acids of the testes showed a marked increase of 5,8,11-eicosatrienoic acid and a decrease in the members of the linoleate family of fatty acids. Gross evidence of essential fatty acid (EFA) deficiency included diminished growth and feed efficiency, and loss of hair. Total lipids, phospholipids, and free cholesterol of testes were found to be decreased, whereas triglycerides followed the reverse pattern. No qualitative or quantitative differences in the fatty acid composition of seminal vesicles were found in the deficient and control groups. Testes of deficient animals showed an extensive degenerative change in the seminiferous tubules; no stage beyond secondary spermatocyte was evident. Glucose 6-phosphate dehydrogenase and Δ5-3β-hydroxysteroid dehydrogenase activity of Leydig cells in both groups showed that these enzymes were present. Male accessory gland weights were significantly reduced in the deficient animals, indicating reduced androgen secretion. Histological examination of the anterior pituitary gland showed signs of degenerative changes in PAS-positive basophilic cells, which appeared to be shrunken and partially degranulated in EFA-deficient rabbits, suggesting that EFA deficiency is accompanied by diminished secretion of the anterior pituitary. There was also an increase in the number of chromophobes and a decrease in acidophil cells. These observations suggest that the degeneration of gonads observed during essential fatty acid deficiency may be due to primary impairment of anterior hypophyseal function.