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Biomedical subjects

G Fink

Publications and source records attributed to G Fink.

At least 271 records · Page 15Linked to original sources
PubMed1977

Effect of oestradiol-17beta exposure on the spontaneous secretion of gonadotrophins in chronically gonadectomized rats.

The effect of oestradiol-17beta (administered in Silastic capsules) on gonadotrophin secretion in long-term gonadectomized rats has been investigated. In female rats, a daily afternoon surge of LH occurred which could be blocked by administering sodium pentobarbitone at 13.00 h. This, together with the fact that there was no significant difference between the LH-response to LH-releasing factor in the morning compared with the afternoon, supports the view that the LH surges are due to a neural rhythm. There was no significant diurnal variation in plasma FSH concentration, but an apparent diurnal variation was disclosed by administering sodium pentobarbitone on alternate days. There was no diurnal variation in plasma gonadotrophin concentrations in male animals implanted with an oestradiol capsule, or in animals of either sex bearing empty capsules.

Animals↗
PubMed1977

A priming effect of luteinizing hormone releasing factor with respect to release of follicle-stimulating hormone in vitro and in vivo.

Pituitary incubation studies were carried out which showed that in the rat luteinizing hormone releasing factor (LH-RF) can exert a priming effect on FSH secretion in vitro. It was found that, as for LH, the effect depends on protein synthesis. The priming effect of LH-RF with respect to FSH could also be demonstrated in vivo; however, the effect was less dramatic than for LH.

Animals↗
PubMed1976

Yeast suppressors of UAA and UAG nonsense codons work efficiently in vitro via tRNA.

A cell-free protein-synthesizing system, containing an S-100 fraction from yeast, ribosomal subunits from Krebs ascites cells, and ribosome initiation factors from rabbit reticulocytes, translates yeast, adenovirus, and rabbit globin messenger RNAs and the RNA from bacteriophage Qbeta. An amber mutation in the Qbeta synthetase gene is suppressed in vitro if the S-100 fraction s from yeast strains carrying amber suppressor mutations. Suppressor SUP6-2 gives 16% suppression, and the recessive lethal suppressor RL-1 gives 50% suppression. Extracts from strain FM6, which has the ochre suppressor SUP4-1, give a longer protein product from the normal synthetase gene at Qbeta with an efficiency of 63%. This implies that UAA is the terminator for the synthetase gene, and that synthesis of this read through protein can be used as an assay for ochre suppression. Suppression in each of these cases is mediated by tRNA, since pufified tRNA is the only fraction from suppressing strains that is required in an otherwise nonsuppressing cell-free system.

Bacteriophages↗
PubMed1976

The development of the releasing factor concept.

After four decades of intense and competitive research, three hypothalamic releasing hormones (formerly factors) have recently been isolated and characterized. These are the decapeptide gonadotrophin releasing hormone (GnRH), tripeptide thyrotrophin releasing hormone (TRH), and the tetradecapeptide somatostatin. Some aspects of these hormones are discussed, and GnRH is considered in greater detail to demonstrate the difficulties involved in fulfilling completely the criteria which determine whether a substance can be accepted as a physiological releasing hormone. A substance immunologically similar to GnRH is present in rat hypophysial portal vessel blood, but, while the amount of this substance released into the portal circulation can be increased significantly by electrical stimulation of the preoptic area, no significant changes occur during the oestrous cycle or after long-term castration. This may be due to interference with the normal secretion of GnRH by the trauma and anaesthesia which necessarily accompany exposure of the pituitary stalk. However, the possibility exists that our preconceived notions regarding the changes in plasma levels of releasing hormones under physiological conditions may be incorrect. Thus it seems likely that changes in the rate of secretion of thyrotrophin is effected by throid hormones modulating the responsiveness of the thyrotrophs to a steady input of TRH. Evidence is presented for the existence of a similar mechanism for gonadotrophin secretion, and the role of steroid hormones and the priming effect of GnRH in modulating the responsiveness of the gonadotrophs is considered. The intrinsic connexions of the hypothalamus, the role of the hypothalamic aminergic systems and the autonomy of the hypothalamus with respect to anterior pituitary control present many problems which will prove difficult to solve.

Androgens↗
PubMed1976

Parameters of electrical stimulation of the medial preoptic area for release of gonadotrophins in male rats.

The release of LH and FSH after the application of an electrical stimulus to the anterior diencephalon of male rats has been studied. The stimulus was applied through either platinum or steel electrodes implanted stereotaxically in animals anaesthetized with urethane. The efficacy of various parameters of stimulation by means of a current consisting of balanced biphasic square waves, was tested by systematically changing the frequency, amplitude and duration of the pulses. The effect of direct current (d.c.) stimulation on hormone release was also examined. The concentrations of the hormones in blood withdrawn from the femoral vein before and at frequent intervals up to 80 min after application of the stimulus were determined by radioimmunoassay. The optimal parameters for the release of LH by square wave stimulation of the medial preoptic area were: frequency, 60 Hz; pulse amplitude, 0-50 mA; pulse duration, 1-00 ms. This stimulus was more effective when applied through steel than through platinum electrodes. Direct current stimulation (15 muA for 10 s) through steel electrodes was most effective of all. When applied through platinum electrodes to the medial preoptic and anterior hypothalamic areas, the optimal square wave stimulus produced significant increases in the concentration of LH after 5 and 10 min respectively. The concentration of plasma FSH in these animals also increased, but the increments were much less than the increments in LH. The magnitude of the respective increases of the gonadotrophins after stimulation of the two brain areas did not differ significantly. Measurement of the milk ejection response to stimulation of the hypothalamo-hypophysial tract in the lactating rat indicated that the spread of the square wave stimulus was no more than 1-5 mm from the electrode tip. The significance of these findings is discussed with respect to the importance of the medial preoptic area in the male rat, the neurones which may be involved in the regulation of gonadotrophin secretion, and the parameters of stimulation used in studying the hypothalamo-hypophysial system.

Animals↗
PubMed1976

Immunoreactive luteinizing hormone releasing factor in rat pituitary stalk blood: effects of electrical stimulation of the medial preoptic area.

Blood was collected from the cut pituitary stalk of male and female rats before and during the application of an electrical stimulus to the medial preoptic area. The plasma was assayed for immunoreactive LH releasing factor (RF) by a double antibody radioimmunoassay using a specific antiserum raised in rabbits against the free acid derivative of the decapeptide LH-RF conjugated to bovine serum albumin. The decapeptide (used as a standard) and pituitary stalk plasma cross-reacted in a similar manner with the antiserum. Stimulation of the preoptic area increased significantly the amount of LH-RF in pituitary stalk plasma in both male and female rats. The increase in LH-RF was linearly related to the strength of the stimulating current, and the amount of LH-RF liberated diminished on cessation of the stimulus. The concentration of LH-RF in pituitary stalk plasma from female rats was significantly greater than that in jugular venous plasma. The magnitudes of the mean increments of LH-RF in pituitary stalk plasma (stimulation minus pre-stimulation values) at various times of the oestrous cycle in female rats suggest that between 18.00 h of dioestrus and 13.00 h of pro-oestrus there is an increase in sensitivity of the LH-RF secretory mechanism to electrical stimulation. However, the increments decreased in magnitude between 13.00 and 18.00 h of pro-oestrus, indicating that the marked increase in responsiveness of the hypothalamo-hypophysial system to electrical stimulation which occurs during this period is due mainly to a change in sensitivity of the pituitary gonadotrophs to LH-RF. The LH-RF in pituitary stalk plasma collected before application of the stimulus was higher at some of the times examined during pro-oestrus than at other times of the oestrous cycle. A higher level of the secretion of the factor may be important for the full development of the priming effect of LH-RF and, consequently, the marked increase in responsiveness of the pituitary gland which occurs during the afternoon of pro-oestrus.

Animals↗
PubMed1976

Priming effect of luteinizing hormone releasing factor elicited by preoptic stimulation and by intravenous infusion and multiple injections of the synthetic decapeptide.

We have investigated whether the priming effect of LH-RF can be elicited by electrical stimulation of the medial preoptic area, or by i.v. infusion or multiple i.v. injections of the synthetic decapeptide. All experiments were carried out on animals anaesthetized with sodium pentobarbitone at 13.30 h. In pro-oestrous rats, the LH response to the second of two electrical stimuli, 15 min in duration and separated by 60 min, was significantly greater than the response to the first stimulus. When synthetic LH-RF was infused at a constant rate for 90 min, plasma LH increased gradually for the first 45-60 min after which it increased markedly. This enhanced secretion of LH did not occur in rats which were infused with the same total dose of LH-RF, either 15 or 75 ng/100 g body wt, over periods of 45 min or less. When a dose of 15 ng LH-RF/100 g body wt was administered in six divided doses by i.v. injections, each separated by 15 min, there was a marked increase in plasma LH after 75 min. The profile of the mean plasma LH concentration in rats subjected to preoptic stimulation for 90 min was similar to that in rats infused for 90 min with LH-RF, but the variation in response was much greater in the stimulated rats. These results indicate that the priming effect can be elicited by endogenous as well as synthetic LH-RF, and that whether LH-RF reaches the pituitary at a constant rate or in a pulsatile manner the factor is capable of significantly increasing the responsiveness of the gonadotrophs. The relevance of these findings with respect to the development of the spontaneous preovulatory LH surge is discussed. A priming effect could not be elicited by constant LH-RF infusion in dioestrous rats; this supports the view that steroid hormones, especially oestradiol-17phi, determine the magnitude of the effect. The LH response in male rats subjected to i.v. infusion of LH-RF was much lower than in females. Pre-treatment with oestradiol benzoate did not increase the response significantly, suggesting that this sex difference cannot be ascribed simply to low levels of plasma oestrogen in the male.

Animals↗
PubMed1976

Priming effect of luteinizing hormone releasing factor: in-vitro and in-vivo evidence consistent with its dependence upon protein and RNA synthesis.

The aim of this study was to determine whether the priming effect of LH-RF depends upon RNA and protein synthesis. In in-vivo studies saline, actinomycin D, or cycloheximide was administered i.p. 3-5-4h before the first i.v. injection of synthetic LH-RF into pro-oestrous rats anaesthetized with sodium pentobarbitone at 13.30 h. The LH-response to the second injection of LH-RF (given 60 min after the first) was markedly reduced by the inhibitors, but the response to the first injection was not significantly affected. Studies with cycloheximide given i.v. showed that the inhibition of protein synthesis up to the second injection of LH-RF reduced the magnitude of the priming effect, the reduction being greatest when the inhibitor was administered up to 30 min after the first LH-RF injection. Pituitary incubation studies showed that the priming effect could also be elicited in vitro and that it could be significantly reduced by actinomycin D, cycloheximide and puromycin. As in vivo, the inhibitors had relatively little effect on the LH-response to the first exposure to LH-RF. The protein synthesized after an injection of LH-RF may be new LH, and/or a protein(s) concerned with 'activation' of the receptor or release components of the LH-secretory apparatus.

Animals↗
PubMed1976

Immunoreactive luteinizing hormone releasing factor in pituitary stalk blood from female rats: sex steroid modulation of response to electrical stimulation of preoptic area or median eminence.

The effects of sex steroid hormones on the responsiveness of the neural mechanism responsible for the secretion of LH-RF have been examined in the female rat. Responsiveness was determined at pro-oestrus by measuring the increments in immunoreactive LH-RF of pituitary stalk blood produced by electrical stimulation of the medial preoptic area or median eminence. Ovariectomy on the morning of dioestrus reduced the LH-RF response to preoptic stimulation while oestradiol benzoate (OB) or testosterone propionate (TP) administered immediately after ovariectomy significantly augmented the response. The facilitatory effect of TP was possibly due to its conversion to an aromatized derivative since 5alpha-dihydrotestosterone monobenzoate was ineffective. Progesterone did not facilitate preoptic responsiveness, and, when administered to animals ovariectomized at 12.00 h of pro-oestrus, reduced the LH-RF response at 18.00 h the same day. Stimulation of the median eminence produced a significantly greater increment in LH-RF than stimulation of the preoptic area. The facilitatory action of OB on the LH-RF response was less marked for median eminence compared with preoptic stimulation. The administration of ICI 46474 at 17.00 h of dioestrus did not reduce preoptic responsiveness on the morning of the next day, suggesting that this compound does not act as an 'antioestrogen' at the level of the preoptic area.

Animals↗
PubMed1975

Histochemical, ultrastructural and hormonal studies on the pars distalis of the echidna (Tachyglossus aculeatus).

There were no consistent significant differences between the concentrations of luteinizing hormone (LH) and adrenocorticotrophin (ACTH) in the rostral compared with the caudal zone of the echidna pars distalis. This suggests that LH is secreted by cells containing S-type granules (probably corresponding to secretory vesicles 200-300 nm diameter) which are distributed throughout the gland. Some of the cells containing vesicles 100-200 nm diameter, seen in small numbers in both zones of the gland, may be responsible for the secretion of ACTH. The concentration of pituitary LH is in the range of that found in eutherian mammals, but the concentration of ACTH is lower than that reported for other vertebrates, and this may be linked causally with the remarkably low rate of corticosteroid secretion in the echidna. The absence of significantly increased levels of pituitary LH and ACTH in a chronically orchidectomized and adrenalectomized animal adds to other evidence which suggests that mechanisms involving a negative feedback of steroid hormones on the hypothalamo-hypophysial axis may not be fully developed in the echidna.

Adrenalectomy↗
PubMed1975

The catecholamine-containing tubero-infundibular system and the control of luteinizing hormone release in the rabbit.

As determined by fluorescence histochemistry, the distribution of catecholamine-containing neurons in the hypothalamus of the female rabbit is similar to that seen in the rat. The fluorescence appearance of the hypothalamus was not appreciably different from normal at 0.25, 1, 4 or 24 h after mating, but in animals in which the synthesis of catecholamines was inhibited by the administration of the tyrosine hydroxylase inhibitor, H44/68, the number of fluorescent neurons seen in the nucleus periventricularis arcuatus following copulation was markedly reduced. However, the concentrations of luteinizing hormone (LH) in serum and in the pituitary glands of mated and unmated animals treated with H44/68 were not significantly different from those found in the corresponding control animals. This, together with the fact that ovulation followed mating in drug-treated rabbits suggests that a normal level of catecholamines in the tubero-infundibular system is not essential for the secretion of the amount of LH necessary for ovulation.

Animals↗
PubMed1975

Mitochondrial assembly in respiration-deficient mutants of Saccharomyces cerevisiae. IV. Effects of nuclear amber suppressors on the accumulation of a mitochondrially made subunit of cytochrome c oxidase.

Earlier studies from this laboratory have shown that cytochrome c oxidase from bakers' yeast contains seven subunits, three of which are made in the mitochondrion (Mason, T. L., and Schatz, G. (1973) J. Biol. Chem. 248, 1355). Moreover, a cytochrome c oxidase-less yeast mutant (pet 494-1) was isolated which lacked one of the mitochondrially made subunits (Ebner, E., Mason, T. L., and Schatz, G. (1973) J. Biol. Chem. 248, 5369). Surprisingly, the mutated gene was localized in the nucleus. The results presented here demonstrate that this mutant phenotype can be suppressed by nuclear amber suppressors which affect translation on cytoplasmic ribosomes. This fact was established by two methods, (a) By constructing pet 494-1 strains possessing various amber and ochre markers, isolating respiring revertants from these strains, and demonstrating co-reversion of the amber (but not of the ochre) markers. (b) By coupling the pet 494-1 allele with the well characterized amber suppressor gene SUP 4-3. These data show that suppressor genes located on nuclear chromosomes may control the accumulation of a mitochondrially synthesized polypeptide. The present results also allow some tentative conclusions about the mechanism of the pet 494 mutation. Because it is highly unlikely that the cytoplasmic and the mitochondrial translation system share a common suppressor, the pet 494 locus probably does not code for the missing mitochondrially made subunit, but for a cytoplasmically made protein. This as yet unidentified protein seems to control the synthesis or the integration of the mitochondrially made subunit. Nuclear suppressor genes may thus be useful tools for studying the role of cytoplasmic protein synthesis in mitochondrial formation.

Alleles↗
PubMed1975

Altered sexual development in male rats after oestrogen administration during the neonatal period.

Male rats given 250 mug oestradiol benzoate by subcutaneous injection on Day 4 of postnatal life showed a marked delay in the onset of the pubertal increase in the weight of the testes and seminal vesicles and in spermatogenesis but not a complete failure of sexual development. The increase in plasma testosterone concentration at puberty was also delayed in oestrogen-treated males but the eventual increase in seminal vesicle weight was closely related in time to the delayed increase in plasma testosterone concentration. Both plasma LH and FSH concentrations were reduced for about 10 days after oestrogen administration as compared to control values. After 22 days of age, plasma LH concentration did not differ significantly from the control values. The plasma FSH concentration of the oestrogen-treated males showed a delayed rise to values equal to or higher than those of controls of the same age. The delayed rise in plasma FSH concentration in the oestrogen treated males preceded the delayed rise in plasma testosterone in these animals. The decrease in plasma FSH concentration from the high prepubertal values to the lower values in adults occurred at different ages in the control and in oestrogen-treated rats but in both groups the decrease occurred as plasma testosterone levels were increasing and the first wave of spermatogenesis was reaching completion. The increase in plasma FSH concentration after castration was reduced in oestrogen-treated males during the period throughout which FSH levels in the intact animals were subnormal but the levels in oestrogen-treated males castrated after the delayed rise in FSH had occurred did not differ from control values. It is suggested that the delayed sexual maturation of male rats treated with high doses of oestrogen in the neonatal period is related principally to abnormalities in the secretion of FSH.

Animals↗