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L Tyrey

Publications and source records attributed to L Tyrey.

At least 37 records · Page 2Linked to original sources
PubMed1984

Effects of delta-9-tetrahydrocannabinol on reproductive neuroendocrine function in the female: animal studies.

The rat experimental model has been utilized to demonstrate pronounced suppressive effects of THC on the secretion of both LH and PRL, a point of considerable interest since the tonic secretions of these two hormones are regulated in opposite fashions, that of LH requiring active stimulation, and that of PRL, continued inhibition. Moreover, both the tonic and surge modes of secretion of both hormones are inhibited or completely blocked by THC action even though these different secretory modes are presumed to be governed by different CNS regulatory mechanisms. The most direct explanation for this broad inhibitory capability of THC would be direct inhibitory action on the pituitary cells secreting LH and PRL. However, experimental evidence drawn from the rat model, consistent with that from other species, provides no support for the possibility of direct pituitary inhibition of significant consequence. Instead, the evidence strongly favors the hypothesis that THC exerts its neuroendocrine action centrally and thereby influences pituitary function through alterations in the release of hypothalamic hormones into the hypophysial portal circulation. With the evidence favoring a central neuroendocrine mechanism for THC action, the rat model becomes particularly valuable because of the enormous body of information already available regarding neuroendocrine function in that species. Initial experiments with the rat have failed to provide evidence supporting the possibility of direct THC action on the hypothalamic neurosecretory neurons terminating in the median eminence.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

Intensive inpatient therapy and survival in gestational trophoblastic disease.

Metastatic gestational trophoblastic disease may be categorized into "good prognosis" and "poor prognosis" groups on the basis of the level of the pretreatment human chorionic gonadotropin titer, the location of metastases, the duration of disease, type of antecedent gestation, and the response of prior therapy. One hundred twenty-six patients with metastatic disease were treated from 1966 through 1979. All patients were treated as inpatients. Sixty-three "good prognosis" patients required an average of 65 days of intensive inpatient chemotherapy and all achieved sustained remission. Sixty-three "poor prognosis" patients were treated. Thirty-eight patients achieved sustained remission after an average of 112 days of intensive chemotherapy. Twenty-five patients (40%) succumbed to disease, after an average of 162 days of therapy. The probability of successful outcome of therapy falls rapidly after 150 days of treatment. Toxicity and deaths are reviewed.

Chorionic Gonadotropin↗
PubMed1983

Comparable surges of luteinizing hormone induced by preoptic or medial basal tuberal electrical stimulation in spontaneously persistent estrous or cyclic proestrous rats.

A previous report demonstrated in cyclic proestrous rats electrically stimulated in the medial preoptic area (MPOA) or the arcuate nucleus-median eminence (ARC/ME) region a close parallel in the progressive increase of serum LH with increasing stimulation time. The present report compares the LH surges induced in middle aged spontaneously persistent estrous (SPE) rats by electrical stimulation of the two regions. Electrical parameters were those previously used. In Series I, MPOA stimulation of SPE rats for 60 min or ARC/ME stimulation for 45 min produced serum LH concentrations 60 and 90 min after stimulation began that were essentially identical to those in proestrous rats similarly treated. In Series II, stimulations were prolonged to 120 min to determine whether LH would continue to rise with the longer stimulation. These rats were all chosen from one shipment and all were born on the same day. Sequential blood samples were taken before stimulation and 60, 90, 120, and 150 min after stimulation began. SPE rats were stimulated in either the MPOA or the ARC/ME and, for comparison, a few proestrous rats that had remained cyclic were stimulated in the MPOA. LH concentrations in these cyclic rats rose more abruptly than in the previous study to amounts significantly higher at both 60 and 90 min, but by 120 min the respective means were not significantly different. In the SPE rats, the 60-min LH levels resembled those in Series I. They continued to rise during the second hour, but only to average levels approximately half those attained in proestrous rats stimulated for 120 min. The comparative increments in MPOA-stimulated and ARC/ME-stimulated rats were similar, although all means in the latter were somewhat higher. The results agree with previous indications that stimulation of either the MPOA or the ARC/ME activates the rostral or caudal portions of a unitary preoptic-tuberal system. Although the tendency of SPE rats to release smaller amounts of LH may result from age-related lowered pituitary responsiveness to LHRH, only future study can determine whether a given degree of preoptic-tuberal stimulation releases equivalent amounts of LHRH in SPE and proestrous rats. Nevertheless, the absence of spontaneous LH surges in SPE points to a primary deficiency in control mechanisms impinging on the preoptic-tuberal system or in its responsiveness thereto.

Animals↗
PubMed1983

Demonstration of intracellular and secreted forms of large human chorionic gonadotrophin alpha subunit in cultures of normal placental tissue.

Free human chorionic gonadotrophin (hCG) alpha-subunit in tissue extracts and incubation media of normal placentae before and after four days of culture was investigated by Sephadex G-100 chromatography. Prior to incubation, tissue extracts of first-trimester and term placentae contained a large form and a small form of alpha-subunit relative to a reference urinary hCG alpha-subunit preparation. The large alpha-subunit comprised 30.6 +/- 1.4 per cent s.e.m. and the small alpha-subunit, 66.9 +/- 4.1 per cent of total intracellular alpha-subunit. After 96 h of incubation, the large alpha-subunit comprised 77.6 +/- 9.8 per cent of the total intracellular alpha-subunit, and the small 21.0 +/- 8.1 per cent. The incubation medium contained a single form of alpha-subunit which eluted with a larger apparent molecular weight than the urinary hCG alpha-subunit. Following neuraminidase treatment, the large alpha-subunit from tissue extracts eluted as a smaller molecule in the position of the urinary hCG alpha reference. A change in Ve/Vo of the small alpha-subunit was not detected. Identical neuraminidase treatment of the large alpha-subunit from incubation medium resulted in an increase in the Ve/Vo, but the large alpha-subunit continued to elute from Sephadex G-100 before the urinary hCG alpha-subunit. However, large alpha-subunit from culture medium did elute in the position of urinary hCG alpha following mild acid hydrolysis. These studies demonstrate that a large form of alpha-subunit is present in first-trimester and term placental tissue both before and after incubation in vitro and that the large form of alpha-subunit is secreted by the normal placenta. The differential effects of neuraminidase treatment on the intra- and extracellular forms of large alpha-subunit coupled with our findings from acid hydrolysis of the extracellular form suggest that alpha-subunit secreted into the culture medium may contain additional carbohydrate residues not present on the intracellular form.

Choriocarcinoma↗
PubMed1982

Treatment of nonmetastatic gestational trophoblastic disease: results of methotrexate alone versus methotrexate--folinic acid.

Two treatment regimens for nonmetastatic gestational trophoblastic disease are compared in this retrospective study. The course of 39 patients with nonmetastatic gestational trophoblastic disease treated with methotrexate alone is contrasted to that of 29 patients with nonmetastatic gestational trophoblastic disease who were treated with methotrexate alternated with folinic acid. Of those patients initially treated with methotrexate alone, 7.7% developed methotrexate-resistant disease and required a change in chemotherapy for induction of remission. In contrast, 27.5% of patients initially treated with methotrexate and folinic acid developed methotrexate-resistant disease and required a change in chemotherapy to achieve remission. Ultimately, remission was achieved in all patients. Methotrexate as single-agent chemotherapy was found to be consistently more toxic than methotrexate alternated with folinic acid. It is concluded that methotrexate with folinic acid at the dosage used in this study, while less toxic than methotrexate alone, is less effective than methotrexate alone in the induction of remission of nonmetastatic gestational trophoblastic disease.

Choriocarcinoma↗
PubMed1982

Effects of (-)-trans- delta 9-tetrahydrocannabinol on serum prolactin in the pseudopregnant rat.

Groups of pseudopregnant rats were injected intravenously with (-)-trans- delta 9-tetrahydrocannabinol (THC) to determine its effects on serum prolactin (PRL) and the maintenance of pseudopregnancy. A single injection of 4 mg THC/kg BW at 2400 h on the first day of leukocytic vaginal smears of pseudopregnancy (D-1) delayed the ensuing nocturnal PRL surge for approximately one hour. When THC (1.0 mg/kg BW) was administered hourly from 2400 h on D-1 through 1700 h on D-2, the nocturnal surge was blocked and serum PRL levels were suppressed until 0600 h on D-2, but not thereafter. Neither treatment altered the duration of pseudopregnancy. These results indicate that the nocturnal surge secretion of PRL during early pseudopregnancy in the rat is sensitive to THC suppression, but that this suppression is not adequate to influence the duration of pseudopregnancy. The mechanism through which THC exerts this action remains unknown.

Animals↗
PubMed1982

Comparison of luteinizing hormone surge responses to ovarian steroids in cyclic and spontaneously persistent estrous rats of middle age.

Female rats of the Charles River CD strain, when 6 to 12 months old, present spontaneous persistent estrus (SPE) in increasing numbers, while others remain cyclic. Apparently as a prelude to SPE, some rats still cycling will fail to ovulate early in response to estrogen or progesterone administration during diestrus. When estradiol benzoate (EB) was given on Day 2 of the 5-day cycle or when progesterone was given on Day 3, the luteinizing hormone (LH) surges, if they occurred at all, tended to be much smaller than the normal surge of proestrus. The normal surges could be equalled only when EB was given on Day 2 and followed by progesterone on Day 3. In SPE rats, progesterone treatment usually induces ovulation only after SPE has been interrupted for a few days and the rat has returned to proestrus-estrus. LH surges induced in that way by progesterone were usually substantial. Thus, the ability of the LH-release apparatus to function had returned within 1 week after interruption of the persistent estrogenic status. Comparison were made of LH surge responses to EB administration in cyclic and SPE rats during pseudopregnancies produced by cervical stimulation (after LH injection of SPE rats) or by daily injection of progesterone. In previously cyclic rats, proestrus-like surges of LH were registered consistently, while in previously SPE rats the levels attained were generally lower. Unexpectedly, if rats were castrated when daily progesterone treatment started, few produced large amounts of LH. This was especially true in the SPE group, 14 of 20 rats failing to show any LH surge. Hence, although capacity to produce the LH surge in response to estrogen + progesterone can return within a few days after SPE cases, some unknown ovarian activity plays an important role. Such activity may also take part in the normal cycle.

Aging↗
PubMed1982

Similarity of luteinizing hormone surges induced by medial preoptic stimulation in female rats blocked with pentobarbital, morphine, chlorpromazine, or atropine.

Adult proestrous rats were subjected to either electrochemical or electrical stimulation of the medial preoptic area after ovulation-blocking dosage with either pentobarbital (PTBL), morphine, chlorpromazine, or atropine. For electrochemical stimulation (ECS), 233 microA anodal DC for 30 sec (7000 mu coulombs) was delivered through a unipolar stainless steel electrode. For electrical stimulation (ES), 750 microA biphasic pulse pairs at 30 Hz, on and off each 15 sec, were delivered through a coaxial platinum electrode, in four 5-min bursts equally spaced during 60 min. In PTBL-blocked rats this stimulus produced LH surges equivalent to those after continuous stimulation for 60 min. Blood was collected 60 and 90 min after ECS or after the start of ES. Mean serum LH concentrations (RIA) maximal at 90 min after ECS, were similar under the four blocking agents (1270-1486 ng/ml serum in terms of NIAMDD LH RP-1). Like-wise, after ES there were no significant differences (P greater than 0.05) among the mean LH levels at 60 min (310-571 ng/ml serum). The 90-min values showed a downward, but not significant, trend in the case of PTBL, chlorpromazine, and atropine plus PTBL. Under morphine an apparent upward trend was due largely to an animal having an especially large increase. With rare exception, full ovulation was evident at terminal laparotomy on the morning after stimulation. Thus, whichever of the several drugs was used, medical preoptic area stimulation with given parameters induced section of comparable amounts of LH. None of the drugs appears to have primary suppressive action on the preoptic-tuberal system, on the availability of LHRH or its release into the portal vessels, on the ability of the pituitary to release LH, or on the ovarian response.

Animals↗
PubMed1981

The function of the corpus luteum of pregnancy in ovulatory dysfunction and luteal phase deficiency.

Relatively little knowledge exists of corpus luteum function in early pregnancy after the successful treatment of ovulatory dysfunction or luteal phase deficiency. To assess the activity of the corpus luteum of such patients, human chorionic gonadotropin (hCG) and 17-hydroxyprogesterone (17-OH-P) levels were determined in serum samples obtained from normal women (44 patients), women with ovulatory dysfunction (10 patients), and women with luteal phase deficiency (7 patients); all determinations were made during conceptive cycles, and sampling continued into the first trimester of pregnancy. There were no statistically significant abnormalities of hCG levels when infertility patients were compared with control patients. According to the premise that 17-OH-P levels reflect corpus luteal function, there appeared to be adequate function in pregnancies after progesterone treatment of luteal phase deficiency. In pregnancies following ovulation induction with clomiphene, the corpus luteum function, on the basis of 17-OH-P levels, was significantly increased in magnitude and duration. These results have clinical implications with regard to supplemental hormone therapy in early pregnancy.

Adult↗
PubMed1981

Delta 9-tetrahydrocannabinol suppression of prolactin secretion in the rat: lack of direct pituitary effect.

The effects of (--)trans-delta 9-tetrahydrocannabinol (THC) on tonic PRL secretion were investigated in long term ovariectomized or hypophysectomized/pituitary-autografted female rats and in flask incubations of anterior pituitary tissue. Intravenous injection of 0.25-8.0 mg THC/kg BW into ovariectomized rats markedly suppressed serum PRL 60 min later relative to control PRL levels. In a second experiment, ovariectomized rats bearing intraatrial cannulae were injected with 0.5 mg THC/kg BW, iv, and serial blood samples were drawn. PRL was significantly suppressed at 10 min, with persistence of the suppression for the duration of the 70-min sampling period in this time-course study. In contrast, the administration of 1.0 mg THC/kg BW, iv, to hypophysectomized/pituitary-autografted female rats failed to influence PRL secretion throughout a 120-min posttreatment sampling period. The apparent inability of THC to directly suppress PRL release from pituitary tissue was further studied by in vitro flask incubations of anterior pituitary tissue. Although a 1-h exposure of rat anterior pituitary tissue to bromocryptine (CB-154; 2.2 X 10(-4) M) suppressed subsequent PRL release, similar exposure to 10(-6) or 10(-4) M THC had no influence. The failure of THC to alter tonic PRL secretion in hypophysectomized/pituitary-autografted rts or PRL release from pituitary tissue in vitro strongly suggests that the central nervous system rather than the pituitary is the site of THC action in the acute suppression of tonic PRL secretion.

Animals↗
PubMed1981

Endocrine aspects of trophoblastic neoplasia.

The trophoblastic cells in both benign and malignant trophoblastic disease secrete a variety of steroid, polypeptide and hormonal agents. Those substances that are known to be elaborated by the neoplastic trophoblastic tissue include hCG, a substance with TSH-like activity, estrogens, progestogens and placental lactogen. The most well characterized of these is hCG, which can be assayed easily. The level of hCG plays an important role in the diagnosis, management and follow-up of patients with trophoblastic disease. Because of this, a sensitive assay that does not cross-react with LH would be ideal. It appears that some of the clinical signs and symptoms seen in these patients (including toxemia, theca lutein cyst, hyperthyroidism and thyrotoxicosis, and galactorrhea) are a direct manifestation or reflection of the level of hCG. There is very little information available at this time on the pathophysiologic role that hCG plays at the cellular level in causing these signs and symptoms. Many questions remain to be answered regarding the role of the other hormones in trophoblastic disease and how they affect the patient. Additionally, very little is known about the potential use of the other hormones in diagnosis, management and follow-up of patients with trophoblastic disease.

Chorionic Gonadotropin↗
PubMed1980

Utility of assay of alpha subunit of human chorionic gonadotropin in management of gestational, trophoblastic malignancies.

All patients who were treated with chemotherapy for malignant gestational trophoblastic neoplasms at the Southeastern Regional Trophoblastic Disease Center and who experienced remission during the period January 1, 1978, through December 31, 1979, were studied in an attempt to determine if the application of an assay for the alpha subunit of human chorionic gonadotropin (hCG-alpha) could predict those patients who would have recurrences. For each patient, the first three weekly serum samples with undetectable HCG by the hCG beta-subunit radioimmunoassay as well as the two preceding samples with detectable hCG were assayed in a homologous hCG-alpha assay. Results reaffirm previous data that the latter assay is useful only in patients receiving oral contraceptives for suppression of pituitary gonadotropin secretion. No patient who has remained in remission had a mean level of hCG-alpha in the three hCG-negative samples greater than 1 ng/ml. Of those patients who had recurrences of trophoblastic disease, two of three had hCG-alpha levels greater than 1.5 ng/ml. Although these data are preliminary, they suggest that the routine measurement of hCG-alpha in patients successfully treated for trophoblastic disease may aid in identification of a group of patients who require additional or more intensive follow-up and/or additional chemotherapy to prevent later recurrences.

Adolescent↗
PubMed1980

delta 9-Tetrahydrocannabinol: a potent inhibitor of episodic luteinizing hormone secretion.

To determine if delta 9-tetrahydrocannabinol (THC) dosages comparable to those obtainable from marihuana cigarettes suppress episodic luteinizing hormone (LH) secretion, THC was administered to ovariectomized rats in doses of 31.2 to 500 microgram/kg b.wt. THC in doses of 62.5 microgram/kg b.wt. or greater rapidly suppressed episodic LH release and reduced serum LH concentrations by 42 to 68%. The period of suppression ranged from less than 30 min to more than 1 hr and was dose-dependent. These results indicate that acute exposure to relatively low doses of THC significantly disrupts gonadotropic hormone secretion in the rat and raise the question of whether episodic LH secretion in humans might be suppressed subsequent to the use of marihuana.

Animals↗
PubMed1979

The utility of a rapid assay for human chorionic gonadotropin in the management of trophoblastic disease.

The diagnosis and treatment of trophoblastic disease depend upon the reliable measurement of human chorionic gonadotropin (hCG) in serum or urine. The double-antibody hCG beta-subunit assay for serum hCG combines great sensitivity, specificity, and precision but requires 36 hours to yield results. This investigation sought to increase the efficiency and total assay volume capabilities of our laboratory through the development of rapid hCG assay to augment the slower beta-subunit system. Two separate rapid hCG assays were examined--a double-antibody radioimmunoassay and a radioreceptor assay. The double-antibody assay took 5 hours to complete, while the radioreceptor assay could be completed with 3 1/2 hours. One hundred serum samples from patients with trophoblastic disease were assayed for hCG in the beta-subunit radioimmunoassay and in both rapid assay systems. No differences in results produced by the rapid double-antibody and the hCG beta-subunit assays were noted; however, results from the radioreceptor assay were significantly different (p less than 0.05) from those obtained in the beta-subunit system.

Chorionic Gonadotropin↗