Showing papers in "Endocrinology in 1959"

Organizing action of prenatally administered testosterone propionate on the tissues mediating mating behavior in the female guinea pig.

Abstract: The sexual behavior of male and female guinea pigs from mothers receiving testosterone propionate during most of pregnancy was studied after the attainment of adulthood. As a part of the investigation, the responsiveness of the females to estradiol benzoate and progesterone and to testosterone propionate was determined. The larger quantities of testosterone propionate produced hermaphrodites having external genitalia indistinguishable macroscopicalty from those of newborn males. Gonadectomized animals of this type were used for tests of their responsiveness to estradiol benzoate and progesterone and to testosterone propionate. The capacity to display lordosis following administration of estrogen and progesterone was greatly reduced. Male-like mounting behavior, on the other hand, was displayed by many of these animals even when lordosis could not be elicited. Suppression of the capacity for displaying lordosis was achieved with a quantity of androgen less than that required for masculinization of the exte...

Visualization of steroid-3beta-o1-dehydrogenase activity in tissues of intact and hypophysectomized rats.

Abstract: Dehydrogenation of dehydroepiandrosterone, a 3β-hydroxysteroid, is demonstrable in all types of steroid-producing cells in the rat adrenal gland, ovary and testis, as well as in some of the oviduct epithelium, when sections are incubated in a phosphate buffer (pH 7.1–7.4) solution containing substrate, propylene glycol, DPN, nicotinamide and the tetrazolium salt, Nitro-BT. No activity toward this substrate is evident in liver or kidney. After cold acetone treatment, activity is severely inhibited in the follicular theca interna but not in the other sites. Steroid-3β-ol dehydrogenase appears more labile than the widely-distributed DPN-dependent dehydrogenase, lactic dehydrogenase. Enzymatic activity remains conspicuous in rat ovary and adrenal cortex after hypophysectomy, declining after 1–2 months only in those residual steroid-producing cells that have become severely atrophied (ovarian interstitial cells, inner zones of the adrenal cortex). Treatment with ACTH restores adrenocortical activity in long-te...

Neuroendocrine correlates of changes in brain activity thresholds by sex steroids and pituitary hormones.

Abstract: A neurophysiological study has been made in rabbits of the effects of sex steroids and pituitary and placcntal hormones on sex behavior and pituitary function as related to changes in thresholds of two opposing cerebral systems: the EEG arousal threshold involving the brain stem rcticular formation (I), and the EEG after-reaction threshold involving the rhinencephalon and hypothalamus (TI). In the estrous or estrogen-primed female rabbit, progesterone at first lowers both thresholds for a few hours and subsequently elevates them to supranormal levels until withdrawal or rebound brings them clown again. The early phase is related to estrus and a lowered threshold of pituitary activation, whereas the elevated thresholds correlate with anestrus and pituitary inhibition. Testosterone, certain pituitary and placental hormones, seasonal influences and even prolonged treatment with female sex steroids affect the two thresholds differentially. Relating the effects on thresholds to behavior and to known thresholds...

Inhibition of the development of the bursa of Fabricius in the embryos of the common fowl by 19-nortestosterone.

Abstract: 0.63 mg. of 19-nortestosterone in 0.1 ml. of corn oil, when injected into the fertilized eggs of the white leghorn hybrid strain of chickens, “Wisco-white,” on the 5th day of incubation, completely inhibits the development of the bursa of Fabricius in both sexes. In the normal chick the bursal primordium appears as a proliferated epithelial mass dorso-caudal to the embryonal cloaca on the 5th day of incubation. By 168 hours of incubation it forms a tubular structure; its terminal end enlarges into a bursal vesicle on the 10th day and becomes lymphoidal by the 15th day. The bursa is fully formed and lymphoidal in 17- day old chick embryos. In 19-nortestosterone-treated embryos the bursal primordium becomes highly vacuolated. Later it remains as a convoluted, short duct without forming the bursal vesicle. Thus the hatched chicks arc bursaless. The secondary effects of this hormone on the rectal complex are the stunted growth of the ventral anal lip, increase of musculature in the dorsal lip and an attenuate...

Induction of behavioral and electroencephalographic changes in the rabbit by hormone administration or brain stimulation.

Abstract: The EEG after-reaction which ordinarily follows coitus in the female rabbit can be induced by “inhibitory-type” low frequency (5⁄sec), low voltage (001–10V) electrical stimulation, applied through chronically implanted electrodes to the hypothalamus, the olfactory bulb, the septum, the hippocampus or the amygdala Following electrical stimulation at these voltages (too low to induce ovulation), the phase of sleep spindles may start immediately, and the latency of the stage of hippocampal hyperactivity is much shorter than that following coitus The EEG after-reaction occurs “spontaneously” after treatment with placental gonadotropins, HCG and PMS, pituitary gonadotropins, LH and LTH, and neurohypophysial hormones, but the latency is greater than that following electrical stimulation Inasmuch as the effective pituitary hormones arc those whose release mechanisms are activated by coital stimuli, the results are consistent with the hypothesis that the induction of the post-coital afterreaction may be medi

Phase relations of 24-hour periodicities in blood corticosterone, mitoses in cortical adrenal parenchyma, and total body activity.

Abstract: Under conditions standardized for analysis of 24-hour periodicity, with light from 06:00 to 18:00 alternating with 12 hours of darkness, corticostcrone in mouse serum undergoes reproducible 24-hour changes, with peak blood levels at about 16:00. Significant differences in phase characterize the 24-hour rhythms in serum corticosterone and in mitoses of cortical adrenal parenchyma; under the same lighting conditions, the peak of the latter occurs at about midnight. The corticosterone rhythm leads in phase the rhythm in gross motor activity and lags behind the eosinophil rhythm, in the absence of intentional stimulation other than daily routine. As compared to the significant change in blood corticosterone level along a 24-hour scale, the immediate effect of audiogenic stimulation upon serum corticosterone is slight. It consists of a small rise following stimulation at the time of the daily “corticosterone low” and is negligibleafter stimulation at the time of “corticosterone high.”The daily rhythm in blood ...

Comparative effectiveness of estrogens on fluid imbibition and growth of the rat's uterus.

Abstract: Five natural estrogens (estradiol-17B, estrone, estriol, equilin and equilenin) and one synthetic estrogen (diethylstilbestrol) were compared as to effectiveness in promoting fluid imbibition and growth of the uterus in 22-day old rats. Graded amounts of each estrogen were injected subcutaneously as a single dose in 0.1 cc. sesameoil and uterine responses observed at intervals up to 72 hours. Both quantitative and qualitative differences were found with respect to dose required for a response and speed, duration, and extent of the reaction. Some estrogens are more effective for fluid imbibition and others more active for growth and superiority for one does not imply superiority for the other. It was found that the minimal dose in micrograms required to produce 33⅓% increase in uterine wet weight at six hours (Astwood unit) is for estradiol, 0.025; estriol, 0.029; diethylstilbestrol, 0.078; equilin, 0.312; estrone, 0.45; and equilenin, 0.546.The dosage required to produce 70% gain in uterine wet weight at ...

Characteristics of behavioral and electroencephalographic after-reactions to copulation and vaginal stimulation in the female rabbit1

Abstract: Electroencephalographic (EEG) changes have been recorded from the brain of the conscious unrestrained female rabbit following coitus and vaginal stimulation. In the estrous estrogen-primed rabbit with electrodes permanently implanted in cortical and deep regions of the brain the following sequence of EEG changes has been observed: (1) A phase of sleep spindles lasting from several seconds to half an hour or more, during which the rabbit appears drowsy if not actually sleeping. (2) A phase of “hippocampal hyperactivity” characterized by an 8⁄sec. high amplitude synchronous EEG record from the hippocampus and its projections. During this period the rabbit is further depressed behaviorally: its head on the floor, ears retracted, eyes almost closed, pupils contracted, heart and respiratory rates slowed, and its only other motion consisting of twitches of the eyelids and jaw movements. Following this phase, which lasts only a few minutes, the rabbit usually stands and starts eating either food or feces which m...

The fluorimetric determination of corticosterone in rat adrenal tissue and plasma: effect of administering acth subcutaneously1

Abstract: A simple method whereby true tissue blanks are obtained has been proposed for obtaining the absolute amounts of rat adrenal and plasma corticosterone by sulfuric acid induced fluorescence. Sacrificing rats after nembutal anesthesia brings about a 77% increase of adrenal corticosterone when compared to decapitated rats. Following a single subcutaneous injection of ACTH, the rat adrenal corticosterone level rises to a maximum after 2 hours to 1.06 μg. per adrenal from a resting level of 0.48 μg. The plasma level during the first hour after administration of ACTH rises to 53.1 μg. from a control value of 19.4 μg. per 100 ml.

The effects of fasting and of growth hormone administration on plasma fatty acid concentration in normal and hypophysectomized rhesus monkeys.

Abstract: The effects of growth hormone and of fasting on the concentration of plasma nonesterified fatty acids (NEFA) in hypophysectomized and intact monkeys (Macaca mulatta) were studied. NEFA concentration was determined by the method of Dole. Small doses (0.05 nig./kg.) of simiangrowthhormone caused an increase in plasma NEFA concentrations in fasting hypophysectomized and intact monkeys. Bovine and porcine growth hormone preparations were ineffective in this regard as were LTH, TSH, ACTH and Pituitrin. The effect of simian growth hormone was absent or diminished if the animals were allowed access to food during the experiment. Fasting caused a marked increase in plasma NEFA concentrations within a few hours. Hypophysectomized as well as normal monkeys showed increased NEFA concentrations in response to fasting, suggesting that the NEFA mobilization during fasting is not mediated by an increased secretion of growth hormone by the pituitary gland.

Antigoitrogenic and calorigenic activities of thyroxine analogues in rats

Abstract: The relative potencies of more than forty thyroxinc analogues and a soluble hog thyroglobulin extract were established in parallel goiter-prevention and calorigenic assays against the same thyroxine standard. By both methods of assay twelve of the preparations had activities ranging from 5% to 800% of that of thyroxine. The activities, if any, of the remaining analogues were less than 3% of that of the standard. Analysis of area-under-curve and speed of response in calorigenic assays indicated that all the active analogues and soluble thyroglobulin were qualitatively similar with respect to this parameter of thyromimetic function in normal adult male rats. Thyroglobulin was characteristically more active than expected when its potency, relative to thyroxine, was calculated on the assumption that its thyronine-bound iodine, as determined by the Blau, 1935, procedure, was in the form of thyroxine.

Induction of pseudopregnancy in the rat by reserpine and chlorpromazine.

Abstract: Treatment of female rats with reserpine or chlorpromazine interrupts normal estrous cycles. To establish whether this effect is related to the discharge of lutcotropin from the adenohypophysis or to the previously demonstrated inhibition of the ovulatory release of pituitary gonadotropin (LH), the pseudopregnancy response in the normal 5-day cyclic rat was tested. When single subcutaneous injections of reserpine (1 mg./kg.) or chlorpromazine (50 mg./kg.) were given to animals during the proestrous or estrous phase of the cycle, 50–60% of the animals became pseudopregnant as indicated by deciduoma formation following uterine traumatization. In contrast, 100% of the rats treated on the first day of dicstrus became pseudopregnant and gave maximal decidual responses. Prolongation of the diestrus phase also occurred in cyclic animals treated on day 2 or 3 of diestrus, but decidual formation, in response to uterine traumatization, was minimal or absent. Nembutal (35 mg./kg.) administered under similar condition...

Hyperplasia of the adrenal cortical tissue in pacific salmon (genus oncorhynchus) and rainbow trout (salmo gairdnerii) accompanying sexual maturation and spawning

Abstract: A comparative study was made of the histological changes occurring in the adrenal cortical tissue of the Pacific salmon, the sea-run steelhead trout, and the non-migratory rainbow trout at various stages in their life cycles with the purpose of ascertaining whether there exists a relationship between degree of adrenal hyperplasia at spawning and survival thereafter. These three fishes show varying post-spawning outcomes from death of all the salmon to partial mortality in steelhead to usual survival of the rainbow trout. The adrenal cortical tissue, found in the cephalic end of the kidney, consists in the sexually immature fish of small isolated groups of characteristic cells which are usually associated with branches of the cardinal vein. With the onset of gonadal development the adrenal cells begin to increase in number and by the time sexual maturity is reached in the salmon and steelhead, marked hyperplasia is present. The cells of this hyperplastic tissue are larger than those in the immature fish an...

Intestinal absorption of insulin in the rat.

Abstract: The intestinal absorption of insulin in the rat has been investigated. Amorphous zinc-free insulin and proteolytic inhibitors (soybean trypsin inhibitor and diisopropylfluorophosphate) were injected into ligated sections of jejunum and absorption of insulin measured by the concomitant depression of blood glucose. The effect on insulin absorption of previously injected indole-3-acetate was alsodetermined. Diisopropylfluorophosphate (DFP) is effective as a depressant of insulin digestion and biologically active insulin is absorbed in small quantities in the presence of this inhibitor. Soybean trypsin inhibitor is not effective. Intraperoneal injection of indole-3-acetate one hour previous to the intestinal administration of insulin and DFP enhances the hypoglycemic action of absorbed insulin. Using an everted sac technique, insulin was shown to pass through the intestinal wall. This wasdemonstrated by chromatographing the sac contents and by the hypoglycemic action of the sac contents when injected into nor...

Islet hypertrophy in obesity of mice bearing acth-secreting tumors1

Abstract: The weight gain in mice bearing ACTH-secreting anterior pituitary tumors is caused by excessive growth of adipose tissue of normal composition. The islets of obese mice show hypertrophy, hyperplasia, and degranulation of beta cells, the. degree of which is closely related to the extent of the obesity. The islet enlargement is caused by increase in size and number of beta cells. In severe adiposity, marked central cavitation of the islet was observed. Islet hypertrophyalso develops, to a lesser degree, in animals maintained on restricted amounts of food. Despite weight loss, these animals are relatively fat. It istheorized that increased insulin secretion induces adipose tissue growth and obesity in these animals.

The effects of atrial stretch on aldosterone secretion.

Abstract: A study was carried out to determine whether the secretion rates of aldostcrone and of hydrocortisone are subject to regulation by receptors located in the atria of the heart. In dogs, the right or left atrium was stretched with sutures which extended from the atrium to the thoracic wall. Adrenal venous blood was collected and analyzed for aldosterone and hydrocortisone. Following right atrial stretch the aldosterone secretion rate was significantly reduced. However, stretching the left atrium was without effect on the secretory rateof aldosterone. These findings strongly suggest that the secretion ofaldosterone may be regulated in part by stretch receptors located in the right atrium.

The effect of adrenal steroids on peripheral fat mobilization in the rat.

Abstract: The fasting adrenalectomized rat moved more fat out of the epididymal fat depot during a 12-hour fast than did the normal animal. Restoration of cortical hormone (hydrocortisone) at both high and low dose levels elicited a marked inhibition of fat movement out of this depot. The administration of hydrocortisone to intact animals also produced this inhibition. The procedure of sham adrenalectomy caused a significant diminution of fat mobilization from the epididymal depot for at least six days following the laparotomy. This response to trauma has now been observed in another laboratory following a burn stress. There are probably factors other than the release of cortical steroids which mediate this response but an increase in steroid titer appears to alter fat mobilization in this direction. The hypophysectomized animal behaves differently from the adrenalectomized animal in this regard. The amount of fat moved out of the epididymal depot by the hypophysectomized animal during a 12-hour fast was much small...

Effects of hormones on glucose utilization in fasted rats.

Abstract: The permeability of tissues toward glucose was explored in rats under various hormonal and environmental influences. The velocity constant K expressing the rate of disappearance of glucose from blood after rapid intravenous injection of a small load of glucose was critically analyzed as an index of glucose utilization. Acute treatments with large doses of glucagon and hydrocortisone led only to negligible effects on K. One hour after epinephrine injection, the persisting hyperglycemia appeared to be due more to increased liver glycogenolysis than to inhibition of glucose utilization. A marked enhancement of K developed 2 hours after a moderate dose. As expected, severe insulin hypoglycemia was accompanied by a sharp increase in K; this was followed by a drasticdecrease during the restoration to normal of the blood glucose level. A single injection of thyroxin led to a rapid increase in K and to a small degree of hyperglycemia. After pretreatment of the animals with thyroxine, the moderate hyperglycemia pe...

Effects of o,p' DDD on histology and 17-hydroxycorticosteroid output of the dog adrenal cortex.

Abstract: In dogs receiving oral treatment with 2,2-bis (2-chlorophenyl-4-chlorophenyl)- l,l-dichloroethane (o,p' DDD) for periods of 2, 4, and 6 days, the secretion rate of 17-hydroxycorticosteroids was markedly decreased. Histological observations on the adrenal cortex showed that focal degenerative lesions developed first in the zona reticularis, then in the zona fasciculata. No changes were seen in the zona glomerulosa even after 6 days treatment. Morphological changes in the zona reticularis and zona fasciculata were slight after 2 days treatment although there was alreacty a marked reduction in the digitoninprecipitable compounds of these zones. After 6 days treatment, 3β-hydroxy sterols were almost absent from the zona fasciculata and zona reticularis. Distribution of sudanophilic lipids of these zones remained unaltered during this period.

The effect of alterations in thyroid function on the pituitary growth hormone content and acidophil cytology.

Abstract: The pituitaries of female rats subjected to various alterations in thyroid function were examined for changes in hypophyseal growth hormone content and acidophil morphology. Thyroidectomy caused a significant decrease in the amount of growth hormone as well as a decrease in the acidophil granulation and population, whereas subsequent treatment with thyroxine allowed the pituitary structure and growth hormone content to return to normal. The pituitaries of unoperated rats fed a diet containing thyroid powder contained less growth hormone than those from normal controls, and the population and granulation of the pituitary acidophils were decreased. The pituitary growth hormone content of thyroidectomized rats fed a diet containing 2,4-dinitrophenol was increased above thyroidectomy levels, but neither the pituitary cytology nor the hormonal level was restored to normal. The same diet fed to unoperated rats did not significantly alter the pituitary growth hormone levels and structure.

Conversion of c14-testosterone to c14-estrogenic steroids by endocrine tissues

Abstract: The ability of stallion testis, human term placenta and a human feminizing adrenal cortical carcinoma to convert C14-testosterone to C14-labeled estrogenic steroids has been demonstrated. The relationship between this conversion and the biosynthesis of estrogens by these tissues has been discussed.

Histocytologic changes in grafts of rat pituitary on the kidney and upon retransplantation under the diencephalon.

Abstract: Histocytologic comparisons were made, hy means of the periodic-acid Schiff (PAS) and the aldehyde fuchsin (AF) techniques, between pars distalis autografts on the kidney and similar grafts re-transplanted close to the median eminence. Time intervals from transplantation to autopsy ranged from 1 day to 6 months. Transplants to the kidney are severely damaged by the transfer, the functional parenchyma ofthe established grafts apparently being derived from a thin shell of healthy tissue surroundingthe massive central infarct. Reorganization of the graft is essentially complete after 1 week. Normal cytologic differentiation is promptly lost. Large gonadotrophs (PAS+, AF−)are missing, but smaller ones may be found in significant numbers for 2 to 3 weeks; after thatthey are rarely recognized. Thyrotrophs (PAS +, AF+) are prominent during thefirst week, but older grafts usually contain in this category only a few minute, angular basophilesand occasional vacuolated cells thought to be “thyroidectomy cells.” Small...

The effect of growth hormone on the in vitro incorporation of leucine-2-C14 into the protein of rat diaphragm.

Abstract: The in vitro incorporation of DL-leucine-2-C14 into diaphragm protein was investigated. Hypophysectomy decreases and growth hormone stimulates leucine-C14 incorporation in fed and fasted animals. The stimulation of leucine- CM incorporation into diaphragm protein effected by growth hormone was not accompanied by a concomitant increase in Q014. Thyroidectomy, while reducing diaphragm Qo2, did not alter leucine-C14 incorporation.

Stimulatory and inhibitory effects of progesterone on the release of pituitary ovulating hormone in the rabbit.

Abstract: A study of the effects of progesterone on ovulation in the rabbit reveals that the steroid at first facilitates and subsequently inhibits the release of pituitary ovulating hormone. Forty estrous or estrogen-primed female rabbits were treated with 2 ing. progesterone in oil subcutaneously and subjected within 1–4 hours to glass-rod stimulation of the vagina; 11 of them ovulated as compared with only 2⁄30 controls. Mating or intravenous copper acetate, within 4 hours after injection of progesterone, stimulated ovulation in all of 10 estrous rabbits. A few progesterone-treated females ovulated “spontaneously.” The facilitation appeared to depend on synergism of progesterone with estrogen; 10 anestrous animals failed to respond to progesterone and vaginal stimulation by ovulating. Twenty-four hours after treatment with progesterone, 21 initially estrous or estrogen-primed rabbits were allowed to mate; only 14 would permit copulation and 10 of these failed to ovulate. None of 10 estrogen-progesterone-treated ...

Effects of acute and chronic treatments with carbutamide (BZ-55) on obese-hyperglycemic mice and their lean littermates.

Abstract: The acute administration of carbutamide was found to have a hypoglycemic effect in fasted normal mice, while it had no definite effect on the already low blood sugar levels of fasted obese hyperglycemic mice. Chronic oral treatment with carbutamide did not modify the food intake and weight increases of either type of mice during the seven weeks treatment. In obese-hyperglycemic mice no improvement of the “diabetes” was observed, both in fed and fasted states. Lean littermates, whether fasted or fed, showed a reversal of the direction of effect of a single dose. These animals were, rather paradoxically, rendered paradiabetic after four weeks of treatment, and responded to glucagon and growth hormone with a reaction similar to that seen in untreated obesehyperglycemic mice.

An effect of corticotropin on urea formation in adrenalectomized-nephrectomized rats.

Abstract: Corticotropin has been found to share with growth hormone the capacity to diminish the accumulation of blood urea nitrogen consequent to the intravenous infusion of an amino acid solution (protein hydrolysate) into acutely adrenalectomized nephrectomized rats maintained with hjdrocortisone. Milligram for milligram ACTH is as active as growth hormone. The nitrogen retaining action of ACTH is abolished by boiling in 0.1N NaOH but not by more gentle treatment with NaOH. ACTHactivity is destroyed by oxidation with hydrogen peroxide but can be restored by incubation with cysteine, in keeping with other adrenal and extra-adrenal activities of ACTH.Growth hormone activity is not definitely destroyed by H2O2 treatment. It is concluded that the above action of ACTH on nitrogen metabolism is another extra-adrenal action of ACTH which is sharedwith growth hormone but cannot be accounted for by contamination of the ACTH with growth hormone, or vice versa.

Functional zonation of the adrenal cortex: pathways of corticosteroid biogenesis.

Abstract: Direct proof that aldosterone is produced by the glomerulosa of beef and rat adrenals has recently been provided. In the present investigation, the functional zonation of beef adrenal cortex has been further studied in vitro. When progesterone, desoxycorticosterone and corticosterone are added to the incubationmedia of beef adrenal slices they are metabolized in radically different ways depending on whether the slices originate in the glomerulosa (G) or in the fasciculata-reticularis (F.R.). I n the presence of tissue taken from G these steroids increase the production of aldosterone. Desoxycorticosterone increases the formation of corticosterone both in G and F.R. Progesterone enhances the production of hydrocortisone in F.R. only, whereas it increases corticosterone and aldosterone production in G. 21-hydroxypregnenolone increases the production of aldosterone in G and that of corticosterone in both G and F.R. 17α-hydroxyprogesterone and 17α-hydroxy-11-desoxycorticosterone markedly enhance the productio...

Further evidence for mediation by histamine of estrogenic stimulation of the rat uterus.

Abstract: Solutions of histamine dihydrochloride or of a synthetic histamine releasing agent (Compound 48–80) were introduced into the uterine lumen of adult, castrated rats. Within four hours following administration, increases in water content and changes in gross vascular appearance of the organ were produced which were comparable to the maxima induced by intravenous or intraluminal estrogen for the same period of treatment. Intravenously administered cortisol substantially diminished the hyperemia and water imbibition elicited by 4–80 or by histamine. Two of the 4 structurally interrelated antihistamines tested (Benadryl hydrochloride and Chlor-Trimeton maleate), were effective in blocking estradiol-stimulated hydration and hyperemia. These findings are regarded as support for the view that estrogen action, in effecting vasodilation and edema in the rat uterus, is mediated by the local release of histamine. It is proposed that cortisol may antagonize responses to estrogen in the uterus by non-specifically decre...