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Biomedical subjects

H Kuhl

Publications and source records attributed to H Kuhl.

At least 127 records · Page 7Linked to original sources
PubMed1979

Enzyme kinetic studies and inhibition by oligopeptides of LH-RH degradation in rat hypothalamus and pituitary.

The enzyme kinetic parameters of the degradation of luteinizing hormone-releasing hormone (LH-RH) and L-cystine-bis-(4-nitroanilide) (Cys-NA) by rat hypothalamic (HYP) and pituitary (PIT) extracts and the effect of various oligopeptides on the rate of LH-RH inactivation were investigated in vitro. The 105,000 x g supernatant of 1 rat HYP inactivated 57 microgram LH-RH during a 30 min incubation (Km = 12.4 microM, V max = 2.33 microgram LH-RH/mg protein/min), and of one rat anterior PIT, 48 microgram LH-RH during 30 min of incubation (Km = 12.2 microM, V max = 8.0 microgram LH-RH/mg protein/min). The synthetic substrate Cys-NA competitively inhibited LH-RH degradation with a Ki of 8.5 microM in the HYP and 6 microM in the PIT enzyme preparation. Vice versa, LH-RH also competitively inhibited the cleavage of Cys-NA with inhibition constants of 14 microM (HYP) and 15 microM (PIT) indicating that the 2 substrates are probably cleaved by the same enzyme. The most effective inhibitors of LH-RH degradation were found to be angiotensin-related peptides, neurotensin, bradykinin, and bacitracin. A relatively weak effect was obtained with oxytocin, enkephalin and puromycin. It is concluded that endogenous oligopeptides such as angiotensins, neurotensin, bradykinin, etc., may possibly influence H-RH degradation in the PIT and the HYP. The synthetic substrate Cys-NA may be an appropriate substrate for measuring the activity of an LH-RH-degrading peptidase, which therefore could be classified as arylamidase.

Aminopeptidases↗
PubMed1979

The biological activity of dimeric testosterone, a new long-acting androgen, and of testosterone enanthate in the castrated male rat.

The long-term effect of single intramuscular injections of various doses of dimeric testosterone and of testosterone enanthate into castrated male rats upon serum testosterone, luteinizing hormone (LH), pituitary LH, and on the weight of the seminal vesicles, the ventral prostate and the levator ani muscle, was investigated. The effect of the enanthate was characterized by a rapid onset and a protracted androgenic action and a suppression of serum LH, while the dimeric testosterone brought about only a moderate but very even depot effect. The injection of 5 mg of the dimeric testosterone caused a positive feedback effectu upon LH release for 16 weeks. The results indicate that the dimeric testosterone may exert is hormonal effects as intact ester.

Animals↗
PubMed1979

Inhibitory control of the pituitary LH secretion by LH-RH in male rats.

Luteinizing hormone-releasing hormone (LH-RH) was administered to prepubertal male rats (intact, castrate or castrate-adrenalectomized, 60 g body weight) for 28 days (1 microgram LH-RH/day, s.c.), at a 10-fold physiological dose, as compared to the minimal FSH-releasing dose of 100 ng/rat s.c. In intact rats, serum LH and weight of androgen-dependent organs (vented prostate, seminal vesicles) were reduced after 14 days of treatment. In castrate rats, the postcastration rise in serum LH was abolished by treatment. Pituitary LH content, FSH secretion and prolactin secretion were not suppressed. Hypothalamic LH-RH was increased at 14 and 21 days. In castrate adrenalectomized male rats, LH secretion was also suppressed by 1 microgram LH-RH s.c. x 28 days. The hypothalamic LH-RH content did not increase. The pituitary LH-RH receptor level was not down-regulated after 14 days treatment either in intact or castrate male rats. Pituitary inhibition (LH release) in rats by a supraphysiological dose of LH-RH given for 28 days indicates that the optimal regime for chronic treatment has to be determined by monitoring LH release at regular intervals. Direct pituitary inhibition by LH-RH may explain some of the unexpected antifertility effects observed with high doses of LH-RH.

Adrenal Glands↗
PubMed1979

Interaction of [125I]LH-RH and other oligopeptides with plasma membranes of rat anterior pituitaries.

The specific binding of [125I]LH-RH to isolated plasma membranes of rat pituitaries was investigated. The binding process was found to be highly specific, temperature-dependent and saturable. The dissociation constant as caluclated by three different methods was approximately 1.3 . 10(-8) M, indicating a single type of binding sites. Maximal binding capacity was 1 . 10(-12 moles/mg protein (= 2 ng LH-RH/pituitary gland), and the number of binding sites was calculated to be 6 . 10(11) per mg membrane protein (=1 . 10(10) binding sites/pituitary gland). When diluted with ice-cold buffer the dissociation of specifically bound LH-RH occurred very rapidly (half-life 3.17 min) with a rate constant of 0.219 min-1. The dissociation process followed first-order kinetics. Specificity of binding was demonstrated by dose-dependent competition of unlabelled LH-RH, the highly potent analogue D-glutamine-(cyclohexyl)6-LH-RH-nonapeptide-ethylamide and the fragment of an analogue (6-D-Ser(TBu))-LH-RH-(3-9)-heptapeptide-ethylamide with the binding [125I]LH-RH, while angiotensin I, II, oxytocin and bacitracin did not compete. The affinities of LH-RH and the analogue to the binding sites of the pituitary plasma membranes were not consistent with the respective biological activities.

Angiotensin I↗
PubMed1979

Effect of sex hormones on HL-RH-degrading hypothalamic enzyme system during estrus cycle in rats.

Basal activity of L-cysteine arylamidase, an LH-RH-degrading enzyme, was determined in the hypothalamus of rats at 4 h intervals throughout the 4-day estrus cycle. The activity of the enzyme system fluctuated during the four estrus stages in a circadian rhythm with maximal values in the night and lowest values at noon. The injection of increasing doses of estradiol-17 beta at various estrus stages caused a moderate stimulation of enzyme activity with no relationship to endogenous hormone levels or estrus stage. The highest activation of the hypothalamic enzyme in response to the application of progesterone occurred at such periods of the cycle when endogenous plasma progesterone is known to be low, and vice versa. When luteinizing hormone or prostaglandin E2 were injected i. v. during the various estrus stages maximal stimulation could be observed at diestrus. The LH-RH-degrading L-cystine arylamidase in the hypothalamus of the rat seems to play a modulating role in the regulation of the tonic LH release during the estrus cycle, but apparently does not influence the events governing the preovulatory LH-peak.

Aminopeptidases↗
PubMed1977

Acute effects of low doses of clomiphene upon LH release in ovariectomized estrogen-progesterone treated rats.

The acute effects of low doses of clomiphene citrate upon serum LH within the first two hours after the intravenous injection into ovariectomized, estrogen-progesterone blocked rats were investigated. There was a short-lasting elevation of LH release 45--60 min after injection of 2.5 microng clomiphene. A second LH releasing effect occurred within 60 min when 50 microng clomiphene or more were injected. Doses between these two dose levels were not effective. It is concluded that these effects may probably be due to a partial reduction of distinct estrogen receptor sites both in the hypothalamus and in the pituitary which causes a short-lasting decrease of the negative feedback of the circulating estrogens.

Animals↗
PubMed1976

[Effects of a new analogue of LH-RH, D-Ser(TBU)6- EA10-LH-RH, on gonadotropin liberation in males (author's transl)].

Effects on the secretion of gonadotropins by D-Ser (TBU)6-EA10-LH-RH were investigated in 7 male volunteers without known endocrine disturbances. One week after subcutaneous injection of 100 mug of LH-RH the probands were given 5 mug of the LH-RH analogue subcutaneously into the abdominal wall. LH, FSH and testosterone concentrations were estimated in the serum and compared with each other at varying intervals after each injection. LH-RH caused a marked increase of the LH content in serum after 20 minutes with a maximum after 40 minutes. The effect of the analogue occurred with a delay. After 40 minutes an LH level was reached which still persisted 6 hours later. Contrary to LH there were considerable individual differences in serum FSH levels. In the initial phase after injection of LH-RH and LH-RH analogue that increase of the FSH level in serum was almost parallel. However, the analogue showed a marked depot effect. Serum concentrations of testosterone showed no significant changes after administration of the releasing hormones. D-Ser(TBU)6-EA10-LH-RH is approximately 20 times effective as LH-RH. A dose of 5 mug is effective for 6-8 hours.

Abdominal Muscles↗
PubMed1976

A new class of long-acting hormonal steroid preparation: synthesis of dimeric androgenes coupled at C3-C3 and C17-C3 and of an androgen-progestogen combination.

3beta-Hydroxy-4-androsten-17-one was prepared from 4-androsten-3,17-dione according to the method of Klimstra and Colton (1) and dimerized by means of esterification with succinic acid. The reduction with lithium-tri-t-butoxyaluminium hydride gave a testosterone derivative coupled between C3-C3 which showed after a single injection of 10 mg a protracted but relatively weak androgenic effect in castrated male rats. The direct esterification of testosterone hemisuccinate with 4-androsten-3beta, 17beta-diol gave the testosterone derivative coupled between C17-C3 which showed a more even and more protracted time response curve than testosterone enanthate. The testosterone-ethynodiol succinate also coupled between C17-C3, showed an androgenic depot-effect similar to that of the dimeric C17-C3 testosterone derivative.

Animals↗
PubMed1976

Oligomeric oestradiol esters: a new class of long-acting oestrogens.

Dimeric and trimeric oestradiol derivatives were administered as single subcutaneous injections into ovariectomized rats and the duration of oestrogenic effect was determined by means of daily vaginal smears. It could be shown that these preparations have a very protracted oestrogenic effect, and their threshold dose is considerably higher as compared to monomeric oestradiol diacetate. A dimeric compound containing one free hydroxy group caused a relatively even response in all animals with a linear relationship between the logarithm of dose and the duration of action. The effect was even more protracted when fully esterified dimeric or trimeric oestradiol succinates were used, but occurred in a more scattering manner. The duration of effect of 40 mug of the trimeric compound exceeded that of the equivalent dose of oestradiol undecylate. It is conceivable that the depot-effect of these oestradiol derivatives is due to delayed elimination.

Animals↗