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Biomedical subjects

Y Koch

Publications and source records attributed to Y Koch.

At least 19 recordsLinked to original sources
PubMed1991

Effect of acute and chronic administration of clonidine on hypothalamic content of growth hormone-releasing hormone and somatostatin in the rat.

Hypothalamic GH-releasing hormone (GHRH) and somatostatin contents were determined in male rats at pre- and mid-pubertal stages following acute (0.15 mg/kg) or chronic (0.1 mg/kg twice daily for 7 days) administration of clonidine. Hypothalamic GHRH content increased markedly during transition from pre- to mid- and late-pubertal stages (2.05 +/- 0.17 vs 3.13 +/- 0.26 and 3.46 +/- 0.20 ng/hypothalamus respectively, means +/- S.E.M.). Hypothalamic GHRH content was markedly decreased 1 h after clonidine administration in mid-pubertal but not in prepubertal rats (3.67 +/- 0.23 vs 2.65 +/- 0.22 ng/hypothalamus). Hypothalamic somatostatin content, on the other hand, decreased in both age groups, although the decrease in the mid-pubertal group was more pronounced (51% and 38% respectively). In addition, the GH responsiveness to clonidine was higher at mid-puberty than at prepuberty. Determination of hypothalamic somatostatin and GHRH content in the chronic experiment 4 h after the last drug administration revealed a marked decrease in GHRH in the mid-pubertal rats and a slight decrease in the prepubertal rats (1.78 +/- 0.32 vs 3.15 +/- 0.31 and 2.01 +/- 0.30 vs 2.35 +/- 0.15 ng/hypothalamus; P less than 0.005 and P less than 0.05 respectively) whereas somatostatin levels were not altered. It is suggested that the clonidine-induced GH secretion is modulated by a chain of events which involves primary stimulation of GHRH release resulting in increased GH secretion which, via a negative-feedback mechanism, triggers an enhancement of somatostatin release which ultimately normalizes the system. This mechanism is age-dependent and reaches full maturity only at the onset of puberty.

Animals↗
PubMed1991

Hypothalamic hormones in milk.

Following a multistep extraction and fractionation of sheep and human milk, immunoreactive and biologically active somatostatin (SS) was demonstrated as a constituent of milk. Milk, in contrast to serum, contains only SS-14-like material and not SS-28. HPLC-purified sheep milk somatostatin was found to inhibit both basal and prostaglandin-induced release of growth hormone from cultured rat pituitary cells. The effect was dose-dependent and similar to that of synthetic SS. In order to determine whether SS or vasoactive intestinal peptide (VIP) can be synthesized by the mammary gland we have looked for SS and VIP messenger RNA in rat glands extracted on different days of lactation. No messages for SS or VIP were detected in the mammary gland, whereas, as expected, hybridization signals for alpha-casein were evident. These results suggest that somatostatin and VIP are not synthesized by the mammary gland and are probably concentrated from blood. In other experiments we have demonstrated that one hour after oral administration of labelled somatostatin to rat pups, about 95% of the neuropeptide, extracted from the stomach, is eluted exactly at the same position as the marker peptide. These results suggest that, in contrast to the adult, somatostatin remains intact in the stomach of the neonate and therefore may be absorbed in a biologically active form.

Animals↗
PubMed1990

Degradation of gonadotropin-releasing hormones in the gilthead seabream, Sparus aurata. I. Cleavage of native salmon GnRH and mammalian LHRH in the pituitary.

The pattern and kinetics of degradation of native salmon gonadotropin-releasing hormone (sGnRH) and mammalian leuteinizing hormone-releasing hormone (LHRH) by pituitary bound enzymes were studied in the gilthead seabream, Sparus aurata. sGnRH and LHRH were incubated for different periods of time with membrane or cytosolic fractions of pituitary homogenates. At the end of the incubation, the degradation mixture was fractionated on reverse-phase high-pressure liquid chromatography. The degradation products were identified by comparing their retention times to those of synthesized GnRH fragments and by analyzing their amino acid composition. The main GnRH degradative activity resides in the cytosolic fraction of the pituitary homogenate. Both sGnRH and LHRH are rapidly degraded by pituitary cytosol, with 78.3 and 87.7% of the peptides, respectively, cleaved after 3 hr of incubation. Maximal degradation of sGnRH occurred at a pH range of 7 to 8. The main initial products of degradation of sGnRH and LHRH are the 1-5, 6-10, and 1-9 fragments. This suggests the involvement of two site-specific peptidases, a Tyr5-Gly6 endopeptidase and a Pro9-Gly10NH2 peptidase or postproline cleaving enzyme. While the 1-6 and 1-9 fragments undergo rapid secondary degradation, the 1-5 is relatively stable. Competition experiments suggest that the endopeptidase cleaving the sGnRH at the Tyr5-Gly6 bond is not specific to the neuropeptide and is probably a general proteolitic enzyme. However, the cleavage at the 9-10 bond has a high degree of specificity to the Pro9-Gly10NH2 sequence found in sGnRH. The two proposed pituitary peptidases of S. aurata have some characteristics similar to those of rat hypophyseal and hypothalamic GnRH cleaving enzymes. No differences are found in hypophyseal GnRH degradative activity between females with occytes undergoing previtellogenesis or advanced stages of vitellogenesis.

Amino Acids↗
PubMed1990

Degradation of gonadotropin-releasing hormones in the gilthead seabream, Sparus aurata. II. Cleavage of native salmon GnRH, mammalian LHRH, and their analogs in the pituitary, kidney, and liver.

The pattern and kinetics of degradation of native salmon gonadotropin-releasing hormone (sGnRH), mammalian luteinizing hormone-releasing hormone (LHRH), and some of their analogs by cytosolic enzymes of pituitary, kidney, and liver were studied in the gilthead seabream, Sparus aurata. The native peptides sGnRH and LHRH are rapidly degraded by all three tissues, LHRH being degraded faster than sGnRH. The kinetics of production of the peptide fragments suggest that initial cleavage of sGnRH and LHRH in the three studied tissues occurs at the 5-6 and 9-10 bonds. This indicates the initial activity of a Tyr5-Gly6 endopeptidase and a Pro9-Gly10NH2 peptidase or postproline cleaving enzyme. Secondary degradation of the main initial fragments (1-5, 6-10, and 1-9) is more intensive in the kidney than in the pituitary or liver. Substitution of the position 6 amino acid glycine by a dextrorotatory (D) amino acid such as in the D-Trp6-LHRH renders the 5-6 bond resistant to cleavage. However, whereas [D-Trp6]-LHRH is intensively cleaved at the Pro9-Gly10NH2 bond by the pituitary, its cleavage at this site by the kidney and liver is slow. This suggests a low activity of the Pro9-Gly10NH2 peptidase in the kidney and liver as compared to the pituitary. When, in addition to the position 6 substitution, the carboxy terminus Pro9-Gly10NH2 is modified to Pro9NET, such as in the [D-Ala6-Pro9NET]-LHRH and the [D-Arg6-Pro9NET]-sGnRH, the 9-10 cleavage site is also blocked, resulting in GnRH analogs highly resistant to degradation. The relationships between susceptibility of the different forms of GnRH to enzymatic degradation by the pituitary, kidney, and liver and their relative biological activities in S. aurata are discussed. We conclude that increased resistance of GnRH analogs to enzymatic degradation contributes to their superactivity.

Animals↗
PubMed1990

The effect of metoclopramide on ovarian responsiveness to gonadotropin administration in patients with severe polycystic ovarian syndrome.

Six patients with poor ovarian response to menotropin after pretreatment with a gonadotropin-releasing hormone analog exhibited improved ovarian responsiveness when metoclopramide was added on days 3, 5, and 7 of the cycle. This was evidenced by a higher number of leading follicles (4.4 versus 0.6), a higher mean of maximal serum 17 beta-estradiol levels (560 versus 178 pg/mL), a shorter duration of menotropin treatment (7 versus 11 days), and fewer ampules of menotropin used (20 versus 37 ampules/cycle) in metoclopramide-treated cycles as compared with control cycles, respectively. Serum prolactin levels reached a maximum of 172 ng/mL within 1 hour after metoclopramide administration and declined to normal range within 6 hours. These results suggest that intermittent increased prolactin secretion may augment ovarian response to gonadotropins.

Drug Therapy, Combination↗
PubMed1989

[Mycoses and AIDS].

The number of patients with AIDS is still growing rapidly. The identification of opportunistic diseases requires special skills in microbiology. The methods for identifying and distinguishing between opportunistic fungi and pneumocystis carinii are introduced.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Estrogen regulation of vasoactive intestinal peptide mRNA in rat hypothalamus.

The participation of gonadal steroid hormones in regulation of the vasoactive intestinal peptide (VIP) gene expression in the hypothalamus was studied using a quantitative densitometric hybridization assay. In the female rat the levels of VIP mRNA were found to be significantly decreased following ovariectomy (4.41 +/- 0.7 arbitrary units of absorbance vs. 8.52 +/- 0.18). This decrease was largely reversed after three days of treatment with estradiol dibenzoate. In contrast to the female rats, no significant change in VIP mRNA levels was observed in the male rats, following orchidectomy. These results suggest a sexual dimorphism with regard to the steroid regulation of hypothalamic VIP gene expression in the rat.

Animals↗
PubMed1988

Steroid regulation of somatostatin mRNA in the rat hypothalamus.

The participation of gonadal steroid hormones in the regulation of the expression of the somatostatin gene in the hypothalamus and cerebral cortex was studied by using a quantitative densitometric hybridization assay which allows the direct measurement of specific somatostatin mRNA levels. The levels of somatostatin mRNA in hypothalamus were found to be significantly decreased following gonadectomy in both male and female rats (67% in males and 75% in females). Moreover, with in situ hybridization histochemistry somatostatin mRNA was similarly reduced following gonadectomy in the dorsal portion of the periventricular region and in the ventromedial nucleus. Estradiol dibenzoate treatment reversed the decrease in somatostatin mRNA in females within 24 h and testosterone treatment reversed the decrease in castrated males. In contrast, there was no significant change in cerebral cortex somatostatin mRNA levels after gonadectomy. These results suggest that sex steroids are involved in the regulation of the somatostatin gene in the hypothalamus, possibly at the transcriptional level.

Animals↗
PubMed1988

Growth hormone releasing factor and somatostatin concentrations in the milk of lactating women.

The concentrations of growth hormone releasing factor (GRF) and somatostatin, two hypothalamic neuropeptides involved in the regulation of growth hormone secretion, were measured in human milk samples. The study was performed in healthy women within 48 h of delivery or during established lactation (between 1 and 64 weeks post delivery). No statistically significant correlation was found between the levels in milk of either of the neuropeptides and the gestational age at birth. However, lower values of GRF (23 +/- 4.7 pg/ml vs. 40.5 +/- 4.9 pg/ml) were found in milk obtained during established lactation than in milk obtained close to delivery. A positive correlation was observed between somatostatin and GRF concentrations in milk. The possible involvement of milk neuropeptides in the control of growth hormone secretion in the neonate, as well as in the regulation of other physiological processes, are evaluated.

Adolescent↗
PubMed1986

Growth hormone releasing factor-like immunoreactivity in human milk.

The presence of immunoreactive growth hormone-releasing factor (GRF) in human milk has been demonstrated. By using sequential high performance liquid chromatography, it has been shown that most of the immunoreactivity co-elutes with the synthetic, hypothalamic-like, GRF (1-40). The concentrations of GRF detected (between 152 and 432 pg GRF/ml milk) exceed several fold its values in plasma.

Chromatography, High Pressure Liquid↗
PubMed1986

Localization of growth hormone-releasing hormone in the human hypothalamus and pituitary stalk.

The localization of the recently identified GH-releasing hormone (GHRH) in the human hypothalamus and pituitary stalk was determined by microdissection techniques and a specific RIA for GHRH. The highest concentrations of GHRH immunoreactivity (IR-GHRH) in the hypothalamus were found in the area of the infundibular nucleus (83 +/- 4 ng/mg protein; average +/- range). Lower quantities were found in other hypothalamic regions. Very high concentrations of IR-GHRH were present in the upper portion of the pituitary stalk (1454 +/- 48 ng/mg protein), and they decreased gradually toward the distal end of the stalk (21 +/- 3 ng/mg). This concentration gradient suggests that the peptide reaches the anterior pituitary mainly by way of the long portal vessels. Somatostatin, the second neuropeptide involved in the regulation of GH secretion from the anterior pituitary, had a pattern of distribution along the pituitary stalk very similar to that of IR-GHRH.

Adult↗
PubMed1985

Immunoreactive and biologically active somatostatin in human and sheep milk.

The presence of immunoreactive and biologically active somatostatin in sheep and human milk has been demonstrated. Milk somatostatin exhibits similar chromatographic behavior to that of synthetic somatostatin-14 on both reversed-phase C18 and cation-exchange high-performance liquid chromatography columns. Milk, in contrast to plasma, contains only somatostatin-14-like material. Milk somatostatin was capable of inhibiting the basal and the prostaglandin-induced release of growth hormone from anterior pituitary cell cultures in a pattern similar to synthetic somatostatin-14. The concentrations of the peptide, as determined by radioimmunoassay, were found to be 113 pg/ml in human milk and 150 +/- 4.8 pg/ml (mean +/- range) in sheep milk. These values are severalfold higher than the corresponding concentration of the peptide in the plasma of these species. These findings are analogous to our previous observations concerning two other hypothalamic hormones, luliberin and thyroliberin [Baram, T., Koch, Y., Hazum, E. and Fridkin, M. (1977) Science (Wash. DC) 198, 300-302]. The high concentration of somatostatin and other neuropeptides in milk implies either an active concentrating mechanism in the mammary gland or an additional extrahypothalamic source for the synthesis and release of these peptides.

Animals↗
PubMed1985

Intracellular pathways of receptor-bound GnRH agonist in pituitary gonadotropes.

Localization of GnRH receptors in rat pituitary gonadotropes was studied by use of 125I-[azidobenzoyl-D-Lys6]GnRH which, upon photolysis, is covalently bound to the receptor molecule. Using high resolution autoradiography, it was found that, after a 90-min incubation of the analog with pituitary cells at 4 degrees C, 93% of the silver grains were associated with the plasma membrane of the gonadotropes. After 45-min incubation of the cells at 37 degrees C, clustering and internalization of the receptor-bound GnRH analog were evident. Silver grains were associated with coated pits, intracellular vesicles, Golgi complexes, lysosome-like structures and secretory granules. The data indicate that receptor-bound GnRH agonist is internalized, at least in part, via coated pits and is subsequently routed to lysosomes where degradation of the hormone-receptor complex may occur. The presence of a considerable amount of silver grains associated with secretory granules may suggest that some of the internalized receptor molecules can escape degradation and be recycled to the cell membrane.

Animals↗