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The pituitary gonadotropin response to the administration of synthetic LH-releasing hormone (LH RH) in 10 patients with renal failure and 5 patients with hepatic insufficiency was determined. The basal plasma LH and FSH levels were either normal or slightly elevated in both groups compared with the controls, but after the administration of LHRH, the peak levels (mean +/- SE mIU/ml) of LH (72.0 +/- 16.6) and FSH (18.7 +/- 4.4) in the patients with renal failure, and of LH (61.5 +/- 20.8) and FSH (13.2 +/- 2.8) in patients with hepatic insufficiency, were not significantly different from those in 11 normal controls (LH, 75.6 +/- 12.0; FSH, 12.4 +/- 2.9). However, significant elevations in plasma gonadotropin levels persisted in these patients during the second and third hours after the administration of LHRH. These studies do not resolve the question of whether the prolonged elevation in plasma LH and FSH levels after LHRH administration is due to enhanced secretion, to a diminished rate of metabolic clearance of LHRH, and/or to the gonadotropins, or both. Evidence from this and previous studies suggests that there may be defects in the secretory functions of both the hypothalamus and pituitary gland in some of these patients.

Synthetic LH-releasing hormone (LH-RH) was administered to 54 healthy adult men in doses of 3, 6, 12.5, 25, 50, 100, 250, and 500 μg. Each dose was given as a single rapid iv injection and, in addition, the doses of 25 and 250 fig LH-RH were given im, sc, and as a 4-hr iv infusion. Plasma gonadotropin levels increased with all of the doses tested and routes of administration, ranging from 700–1400% for LH and 200–600% for FSH. Some subjects in each group also showed a 50–100% increase in the levels of plasma testosterone and 17-OH progesterone.

Synthetic LH-RH was administered to prepubertal, pubertal, and adult human males as a four-hour iv infusion at a dose of 100 μg/m2 body surface. Plasma levels of LH, FSH, testosterone, androstenedione and cortisol were measured by radioimmunoassays. It was found, in general, that adults released the most LH and the least FSH after LH-RH. Some increase in testosterone but not cortisol levels was observed. The exact interpretation of the data depends upon whether the results are expressed as maximal increment in absolute amounts (mIU/ml), maximal increment in percent, or total amount of released hormone. Regardless of the manner of expression, however, the results support the original observation that children as well as adults release gonadotropins in response to LH-RH.

Although the physiological actions of angiotensin have attracted considerable interest, its effects on the maximal renal tubular transport rates for p-aminohippuric acid (PAH) and glucose (Tmpah and Tmg) have not previously been described in any species. This study therefore comprised an examination of Tmpah at three dose levels and Tmg at two dose levels of angiotensin. The Tm of neither substance was reduced. In the course of the experiments, glucose was found to elevate control PAH clearance measurements and to offer some protection against the renal vasoconstrictive effect of angiotensin. It was concluded that angiotensin does not cause focal renal cortical deprivation of blood flow, nor does it interfere with the tubular transport of PAH or glucose. Other aspects of the renal response to angiotensin are altered by glucose.

The role of MSH in man is unknown. Administration of 10 mg synthetic alpha melanocyte-stimulating hormone (MSH) to 5 human subjects resulted in a significant increase in the averaged somatosensory cortical evoked response (AER). This change in the amplitude of the somatosensory evoked response was so marked that it could be seen on single trials of the EEG. The AER further increased during attention. Performance on the Benton Visual Retention Test also improved significantly after infusion of MSH. These findings demonstrate extra-pigmentary effects of MSH in man and suggest an effect upon the attentive process.

Thyrotropin-releasing hormone (TRH) was administered iv to 8 patients with renal failure, 8 normal men, and 5 children. Injection of 1600 μg TRH as a bolus to healthy adults or a smaller dose to children resulted in a normal pattern of TSH release. The prolonged release of TSH which occurred after stat injection of 400 μg TRH to the patients with greatly diminished renal function was similar to that found after a 4-hr infusion of 1600 μg in normal men. In the men receiving the iv infusion, TSH levels began to diminish after 2 hr, despite the continued infusion of TRH for an additional 2 hr. An unexpected increase of hGH was also found in 7 of 8 patients with renal failure after injection of TRH.

3H-Pro-Leu-Gly-NH2, a melanocyte-stimulating hormone release inhibiting factor, was injected into 5 healthy men. A plot of the time of the disappearance of radioactivity in plasm

An analogue of luteinising-hormone-releasing hormone ([D-Leu-6, desGly-NH2-10]-L.H.R.H.-ethylamide) was administered by mouth to thirteen healthy men. In eight men 10 mg of this superactive L.H.R.H. analogue significantly increased mean plasma-L.H. within 45 minutes of administration. This increase was sustained for more than 5 hours. 2 mg of the analogue did not significantly increase plasma-gonadotrophin concentrations in the five men to whom this smaller dose was given. Oral administration of some L.H.R.H. analogues would seem to be effective in releasing L.H. in man.

It was first determined that luteinizing hormone-releasing hormone (LH-RH) obtained from porcine, bovine, and ovine sources was biologically active in man. When the structure of porcine LH-RH was determined, synthetic material was also found active in man. Studies indicated that FSH as well as LH were released from the pituitary into the peripheral circulation by both the natural and synthetic LH-RH. Although blood basal levels of LH and FSH are increased after the menopause a further increase was produced by LH-RH, either naturally or synthetically. In other conditions (Klinefelter's and Turner's syndromes) with naturally occurring elevations of blood levels of LH and FSH, further release was also obtained by both natural and synthetic LH-RH. In subjects pretreated with 200 mg/day clomiphene additional rapid increase was obtained. In patients with pituitary tumors and acromegaly the response was variable. However, 1 patient who did not release gonadotropins after LH-RH did release thyrotropin (TSH) after receiving TSH-releasing hormone. The effects of LH-RH administration on other steroids in the blood are currently being investigated. Routes other than the intravenous administration are being tried, e.g., subcutaneous and intramuscular. It has been found that a child's pituitary can release LH and FSH after administration of porcine LH-RH. In Kallmann's syndrome of hypogonadotropic hypogonadism with anosmia, a small increase of gonadotropin release has been shown after rapid intravenous injection of LH-RH. Long duration of intravenous infusion of LH-RH with 2 supplementary intramuscular injections has produced ovulation in a patient primed with an FSH-containing material (Pergonal). In other experiments patients pretreated with clomiphene had an increased incidence of ovulation. In men with oligospermia only slight improvement has been obtained. Most of the data presented were obtained using highly purified material of porcine origin.

[pyro]Glu-Ser-Gly-NH2 has been reported to release GH. Therefore, this tripeptide was injected iv at a dose of 600 μg into 10 men and women, 3 of whom had acromegaly. Plasma levels of GH, TSH, LH and FSH were measured, but no consistent elevations were found. The results do not support the proposal that [pyro]Glu-Ser-Gly-NH2 is the GH-releasing hormone.

Two analogues of LH-RH as well as pure, natural LH-RH were compared with synthetic LH-RH in normal men. The 9-ethylamide LH-RH caused increments in plasma levels of LH and FSH comparable to those caused by synthetic LH-RH given at double the dose level. About twice the amount of the 5-phenylalanine analogue, as compared with synthetic LH-RH was required to release similar amounts of LH and FSH. Prolongation of action was found in some subjects by the addition of 16% gelatin to the im injections and mean maximum peaks may have been delayed when the 9-ethylamide LH-RH was given as a rapid iv injection. Pure natural LH-RH was as potent as the synthetic decapeptide.

The disappearance of LH-releasing hormone (LH-RH) administered i.v. together with inulin was measured by radioimmunoassay. The half-time disappearance of 3.6 min for LH-RH was significantly shorter than the half-time of 14.2 min found for the inulin. On the assumption that diffusion and distribution into the extracellular space and excretion are quantitatively similar for LH-RH and inulin, the part of the half-life of LH-RH due to metabolic breakdown can be calculated to be about 4.8 min. Peak LH and FSH values were found to occur later. The results suggest that most of the immunoreactive LH-RH is no longer present in the blood at the time of maximal gonadotropin release and that this is because of rapid metabolism as well as diffusion and excretion.

Four analogues of LH-releasing hormone (LH-RH) were injected iv. in normal men at a dose of 25 mug: des-Gly-10NH2-LH-RH ethylamide (9-EA-LH-RH); des-Gly-10-NH2-LH-RH propylamide (9-PA-LH-PH), d-ala-6-LH-RH; and D-Ala-6, des Gly10-NH2-LH-RH ethylamide (D-Ala-6,9-EA-LH-RH). Each peptide tested was found to be more potent than LH-RH in releasing LH and, to a lesser extent, FSH. The times of the peak values of LH after the analogues were similar to LH-RH (about 20 minutes). However, LH as well as FSH levels were considerably delayed in returning to baseline after administration of D-Ala-6,9-EA-LH-RH. The half-time disappearances of the 9-EA and 9-PA analogues could be tested and were found to be similar to that of LH-RH. The increased potency and prolonged duration of action of D-Ala-6,9-EA-LH-RH suggest the potential usefulness of this compound in stimulating ovulation and perhaps spermatogenesis.Luteinizing hormone-releasing hormone (LH-RH), and 4 of its analogues were each tested in groups of 6 normal men. 25 mcg of des-Gly-10-NH2-LH-RH ethylamide (9-EA-LH-RH), des-Gly-10-NH2-LH-RH propylamide (9-PA-LH-RH), D-Ala-6-LH-RH, D-Ala-6, des Gly-10-nh2-lh-rh ethylamide (D-Ala-6,9-EA-LH-RH), and LH-RH were injected iv and the halftime disappearance from the blood of 2 of these analogues as well as LH and follicle stimulating hormone (FSH) levels were determined by radioimmunoassay. The peptides tested were found to be more potent than LH-RH in releasing LH and, to a lesser extent, FSH. The time of the peak values of LH and the analogues was about 20 minutes, however, LH and FSH were delayed in returning to baseline after D-Ala-6,9-EA-LH-RH. 9-EA and 9-PA analogues were similar to LH-RH in halftime disappearances. D-Ala-6,9EA-LH-RH showed increased potency and prolonged duration of action, thus suggesting potential usefulness in stimulating ovulation and perhaps spermatogenesis.

The renal and pressor actions of angiotensin in relation to dose were studied in unanesthetized dogs. Low doses caused depression of urine flow, electrolyte excretion, glomerular filtration rate (GFR), and Cpah. With higher doses, the initial depression of urine flow, GFR, and Cpah was greater, but subsequently these functions rose toward control values. In fact, diuresis occurred, accompanied by natriuresis, chloruresis, and kaliuresis. The natriuresis occurred at a time when GFR was significantly depressed. In longer experiments at high doses it was found that the natriuresis declined after 50 min despite continued angiotensin infusion; however, potassium excretion gradually increased throughout. These results help clarify the confusing literature regarding the effects of angiotensin on renal function in dogs and also support the hypothesis that angiotensin can block tubular sodium reabsorption. The pressor response was found to be proportional to the logarithm of the dose of angiotensin. It was also inversely related to the control blood pressure of the dog.

Previous studies from this laboratory, as well as elsewhere, have indicated that the antrum of the stomach is the chief or sole source of the gastric-secretion-stimulating hormone, gastrin. Complete excision of the gastric antrum in dogs practically abolishes the secretion of gastric juice from a vagusdenervated Heidenhain pouch.1Exclusion of the antrum from the alimentary tract produces a similar reduction in secretion from the Heidenhain pouch, and this is restored if the antrum is replaced in its normal position or transplanted to the duodenum as a diverticulus. Transplantation of the antrum to the colon produces a marked hypersecretion of gastric juice from the Heidenhain pouch. On the other hand, transplantation of similar pouches fashioned from the corpus or fundus of the stomach into the duodenum or colon produces no stimulation of secretion.2If the antrum is converted into a vagus-denervated isolated pouch in an animal also provided with

Introducion En el mes de Enero de este ano se practicaban unas excavaciones por medio de la dinamita, para arranear rocas de construccion en la base del cerro Hamado Penon de los Banos, a cuatro kilometros este de la ciudad de Mexico...

Rústica Tít. de la cub.: Refutación al Restaurador

Plasma prolactin levels were not consistently changed by administration of a dose of synthetic LH-RH which released LH and, to a lesser extent, FSH in 19 normal men. Pretreatment with large doses of estrogen, progesterone, or their combination for three days did not affect the release of prolactin.