Search PubMed⌕ Search

Biomedical subjects

C Weil

Publications and source records attributed to C Weil.

At least 37 records · Page 2Linked to original sources

Evidence of GnRH receptors in cultured pituitary cells of the winter flounder (Pseudopleuronectes americanus W.).

For continued studies of GnRH receptor regulation in the winter flounder, we have developed an in vitro system consisting of cultured pituitary cells dissociated by collagenase. Using immunocytochemical staining methods for gonadotropin, growth hormone, and prolactin, these cell types were represented at the levels of 25, 20, and 19.5% of total pituitary cell population, respectively. Receptors for GnRH were characterized in intact monolayered attached pituitary cells, maintained in RPMI culture medium. The cell GnRH receptor characteristics were compared with those previously described using pituitary homogenates. The cells were capable of binding GnRH in a similar manner on Day 2 or Day 3 of culture, indicating the integrity of GnRH receptors. The specificity of binding was demonstrated since only high doses of cold GnRHa competed with 125I-GnRHa uptake, different peptides being without effect. The specific binding is saturable and the data suggest the presence of a single class of high-affinity (apparent Ka = 1.50 x 10(9) M-1), high-capacity sites (binding capacity = 25.03 fmol/2.5 x 10(5) cells or 242.23 x 10(3) sites/gonadotroph) which is in accordance with the characteristics of GnRH receptors present in homogenates of pooled male and female pituitary glands. All these observations suggest that such an in vitro pituitary cell system would be appropriate for studying GnRH receptor characteristics under different physiological conditions.

Animals↗

Effect of somatostatin on prolactin in rainbow trout (Oncorhynchus mykiss) pituitary cells in primary culture.

To study the control of prolactin secretion in fish, an in-vitro technique using a monolayer cell culture system of rainbow trout pituitary glands was developed. Such secretion was characterized by measurement of both prolactin release and prolactin mRNA content using a trout prolactin cDNA as a probe. This cell culture technique, already used to study the regulation of gonadotrophin secretion in rainbow trout, was further validated by measuring total DNA and protein content. Both parameters appeared to be stable after 2 days of culture. Studying the effect of somatostatin (SRIF) on prolactin cells indicated that a maximal inhibitory effect (62%) was observed after 24 h of treatment. Significant inhibition of prolactin release was obtained for SRIF doses ranging from 50 nM to 1 microM. However, in the same experiment, SRIF was much more potent as an inhibitor of growth hormone release. Short-term (< 12 h) incubation with SRIF did not induce a significant change in prolactin release, whereas growth hormone release was reduced at as early as 1 h after SRIF exposure. SRIF did not have a significant effect on total prolactin content or prolactin mRNA levels, suggesting the absence of an effect on prolactin synthesis. No increase in the magnitude of the inhibitory effect of SRIF was observed when using pituitary cells from immature, mature male or mature female trout. When comparing effects on primary cultures containing cells from the whole pituitary with a prolactin cell-enriched population, SRIF appeared to have the same inhibitory effect on prolactin release, supporting a direct action of SRIF on prolactin cells. These results provide further support for SRIF being a prolactin-inhibiting factor in rainbow trout and acting as a modulator of a dominant stimulatory control of prolactin release.

Actins↗

Development and validation of a highly sensitive radioimmunoassay for chinook salmon (Oncorhynchus tshawytscha) growth hormone.

This study describes the development of a highly specific and very sensitive radioimmunoassay for salmonid growth hormone. Antiserum raised against chinook (Oncorhynchus tshawytscha) GH2, which did not recognize 125I-sPRL and 125I-sGTH (at 1:1000 initial dilution), was able to inhibit growth when injected into rainbow trout (Oncorhynchus mykiss). 125I-sGH2, used as tracer, was not recognized by anti-sGTH or by anti-sPRL. Mammalian GH and ACTH and salmonid GTH, TSH, and PRL did not cross-react in the sGH assay. The inhibition curves for pituitary extracts and plasma from salmonids were parallel to the salmon GH standard, whereas those from carp, tilapia, and catfish showed no significant cross reactivity. The RIA ED90 and ED50 values were 0.2 and 1.5 ng/ml, respectively. Using this RIA for measuring GH release by cultured pituitary cell we observed a strong inhibiting effect of SRIF (10(-6) M) and a stimulatory effect of hGRF (10(-6) M). This RIA allowed us also to detect daily fluctuations in the plasma GH concentration in cannulated rainbow trout.

Animals↗

Cultured pituitary cell GtH response to GnRH at different stages of rainbow trout oogenesis and influence of steroid hormones.

In rainbow trout, a variable in vivo pituitary sensitivity to GnRH has been previously observed, depending on the stage of oogenesis. The purpose of the present work was to study, in vitro, the role of oestradiol (E2) and 17 alpha-hydroxy,20 beta-dihydroprogesterone (17 alpha 20 beta P), respectively, involved in vitellogenesis and in oocyte maturation, upon this variability. The study was performed using primary cultures of whole pituitary cells from animals at different stages of oogenesis and subjected to increasing doses of salmon GnRH (sGnRH) after a 3-day pretreatment with control medium or medium supplemented with the steroid at levels corresponding to those circulating at the time of particular events of the sexual cycle (maturation and vitellogenesis). In control cultures, pituitary GtH responsiveness to sGnRH was maximal at ovulation, since at this time the gonadotrophs were able to respond to 10(-9) M sGnRH, whereas during vitellogenesis and preovulatory stages, the minimal effective dose of sGnRH ranged between 10(-6) and -8 M. We have demonstrated that 17 alpha 20 beta P has a positive or negative effect by acting directly on pituitary cell responsiveness to sGnRH, depending on the stages at which it is applied; its effect is positive during early vitellogenic and preovulatory stages whereas it is negative at the time of ovulation. E2 also increased pituitary responsiveness to sGnRH when applied during early vitellogenesis at low doses, corresponding to circulating levels at the time of ovulation; higher levels of E2, corresponding to circulating levels found during the last stages of vitellogenesis, did not modify pituitary responsiveness but increased cell GtH content.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Cultured pituitary cell GtH response to GnRH at different stages of rainbow trout spermatogenesis and influence of steroid hormones.

Using primary cultures of whole dispersed pituitary cells collected from rainbow trout at different stages of spermatogenesis, basal and GnRH-induced GtH release and cell GtH content were studied in control and steroid-pretreated cultures. Steroid pretreatments were performed for 3 days with 11-ketotestosterone (11KT) and 17 alpha-hydroxy,20 beta-dihydroprogesterone (17 alpha 20 beta p) at levels corresponding to those circulating at the time of spermiation (50 and 20 ng/ml, respectively). In control cultures, basal GtH release and cell GtH content increased with the stage of spermatogenesis in a characteristic pattern as predicted from in vivo results concerning plasma and pituitary GtH contents. The pituitary response to salmon GnRH (sGnRH) also varied as indicated by the decrease in the minimal effective dose of GnRH able to induce a significant GtH release with the advancement of spermatogenesis: 10(-7) M at the spermatocyte stage, 10(-9) M at prespermiation and spermiation. Steroid pretreatments were shown to have a direct effect on pituitary gonadotrophs and particularly on pituitary response to sGnRH, depending on the stage at which they are applied. At the beginning of spermatogenesis both of them induced an increase in GtH release and at prespermiation they have a slight negative effect, significant only with 17 alpha 20 beta P. At spermiation they have no effect except for 17 alpha 20 beta P which increased the response to 10(-8) M of sGnRH. Results are discussed in relation to hormonel changes (gonadotropin and steroid) observed by different authors during the sexual cycle.

Animals↗

Calcium ions as a mediator in GnRH action on gonadotropin release in the common carp (Cyprinus carpio L).

Collagenase-dispersed carp pituitary cells in a perifusion system were used to study the role of calcium ions in the mechanism of GnRH action on the release of maturational gonadotropin (GtH) in fish. The specific calcium chelator EGTA and the calcium antagonist manganese (Mn2+) caused a 40% inhibition in the basal GtH release and completely blocked GnRH-stimulated GtH release. Short-term application of graded doses of calcium ionophore A23187 caused a dose-dependent increase in GtH secretion. A23187 failed to stimulate GtH secretion in the presence of EGTA. Depolarization of the membrane by K+ caused a strong stimulation of GtH release similar to the action of GnRH. Stimulatory action of K+ was inhibited by EGTA. These data suggest a role for extracellular calcium as an intracellular mediator in GnRH-stimulated, as well as in basal, GtH release in carp. The stimulation of GtH release by K+ also indicates that voltage-dependent processes could be involved in this phenomenon.

Animals↗

Involvement of voltage-dependent calcium channels (VDCC) in the action of GnRH on GtH release in common carp (Cyprinus carpio L): comparison with K+ action.

The involvement of different types of voltage-dependent calcium channels (VDCC) in the stimulatory action of GnRH (in comparison with K+) on maturational gonadotropin (GtH) release was investigated using superfused carp pituitary cells. The action of these 2 stimulants was not modified either by D600 or nifedipine (drugs blocking L-type of VDCC). Cadmium (Cd2+), which blocks all types of VDCC indifferently, provoked a dose-dependent stimulation of GtH secretion. Cd2+ action was not altered by addition of sGnRH in any of the doses. Similar results were obtained using K+ as a secretagogue, but only the highest dose of Cd2+ (200 mumol/l) was able to completely block K+ action. Low doses (0.1 and 1 mumol/l) of the L-type VDCC activator BAY-K8644 did not change basal GtH secretion and had no effect on sGnRH-stimulated GtH secretion. Surprisingly, doses (10 mumol/l and higher) of BAY-K8644 evoked dose-dependent inhibition of GtH secretion. On the other hand, a higher concentration (20 mumol/l) of nifedipine provoked a stimulation of GtH release. Our results indicate that the stimulatory action of GnRH and K+ involves activation of a certain type of cadmium-sensitive VDCC (probably T- or N-type VDCC) whereas dihydropyridine and diphenylalkylamine sensitive VDCC (L-type VDCC) does not participate in this phenomenon. The inhibitory action of BAY-K8644 and, on the other hand, the stimulatory action of nifedipine indicate that L-type VDCC probably play a role in other physiological pathways regulating GtH release in carp.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

Use of pituitary cells in primary culture to study the regulation of gonadotropin hormone (GtH) secretion in rainbow trout: setting up and validating the system as assessed by its responsiveness to mammalian and salmon gonadotropin releasing hormone.

To study the regulation of gonadotropin secretion in rainbow trout in vitro, a method for preparing primary cultures of dispersed pituitary cells is described. Cells were dispersed by collagenase 0.1% in Hank's saline solution for 20 hr at 12 degrees and a high yield of viable cells was obtained. Attempts to improve cell functioning were made by varying culture conditions (density of cells initially plated, age of the culture). Cell functioning was assessed by their ability to respond to increasing doses of mammalian and salmon GnRH. Pituitaries were collected from spermiating males whose pituitaries are known to be sensitive to mammalian GnRH in vivo. Using 96-well plates, optimal conditions for good biological activity, are initial plating with 6.2 X 10(4) cells, incubation with GnRH for 24 hr on the third day after plating. In these conditions mammalian analog and salmon GnRH induced an increase in GtH release for doses ranging from 10(-9) to 10(-6) M. The GtH released during the GnRH incubation period does not decrease the sensitivity of the system since addition of 20 ng of GtH at the beginning of incubation does not modify the response profile.

Animals↗

The safety of bromocriptine in hyperprolactinaemic female infertility: a literature review.

The dopamine agonist bromocriptine has been widely used to facilitate pregnancy in hyperprolactinaemic women, with a success rate of 80% in relevant cases. Neither the inappropriate hyperprolactinaemia consequent upon bromocriptine withdrawal after conception nor the relative hypoprolactinaemia caused by treatment throughout gestation appears to affect adversely the course and outcome of pregnancy or the endocrine status of the fetus. No teratogenic effect of bromocriptine has been evidenced in humans, and no disturbances in the physical, psychomotor, and intellectual development of the offspring have been observed. Pituitary-tumor enlargement during closely supervised pregnancies very rarely leads to severe and irreversible complications; both the re-institution of bromocriptine treatment in the event of tumor enlargement and its preventive use throughout pregnancy have been shown to be effective measures. It is interesting, moreover, that a reduction of hyperprolactinaemia, compared with pregestational levels, may be seen after bromocriptine-facilitated pregnancies.

Abnormalities, Drug-Induced↗

The safety of bromocriptine in long-term use: a review of the literature.

This paper reviews the safety data on bromocriptine administration for 1 to 10 years at daily doses of 1.25 to 80 mg in over 1100 patients with pituitary hormone overproduction (mainly from prolactinomas and growth-hormone producing adenomas), at daily doses of 3.75 to 170 mg in over 700 patients with Parkinson's disease, and at daily doses of 2.5 to 20 mg in 28 patients with various other conditions. In addition, information is provided on the safety for mother and child of bromocriptine administered at daily doses of 2.5 to 35 mg throughout gestation (54 pregnancies) or during its later stages (39 pregnancies). The side-effects of long-term bromocriptine treatment are usually no different from those seen during short-term treatment; most of them are relatively benign, and they have been shown in virtually all patients to be reversible. Bromocriptine appears to have no harmful effect on hepatic, renal, haematologic, or cardiac functions. It is considered that a hitherto unknown, severe though rare side-effect of bromocriptine is unlikely to be reported after such long experience.

Acromegaly↗

Antepartum nonstress fetal heart rate monitoring: systematic analysis of baseline patterns and decelerations as an adjunct to reactivity in the prediction of fetal risks.

A total of 1552 antepartum nonstress tests performed during the week before delivery are analyzed with respect to both reactivity and the presence of pathologic baseline patterns (tachycardia, bradycardia, diminished beat-to-beat variability) or decelerations. Correlation with mode of delivery and condition of the newborn infant shows that, irrespective of nonstress test reactivity, the presence of baseline anomalies and/or decelerations is associated with significantly increased perinatal morbidity and mortality. Nonstress test analysis, if systematic, that is, not restricted to reactivity alone, makes it possible to better detect fetuses at high perinatal risk, in which case closer surveillance would be indicated.

Apgar Score↗

Manipulation of the hypothalamo-pituitary gonadal axis in the juvenile rainbow trout: influence of pituitary transplantation and LHRH analogue treatment.

The effect of implanting an extra pituitary containing large amounts of gonadotropic hormone (GtH), combined or not with a luteinizing hormone releasing-hormone analogue (LHRHa) treatment, on GtH levels and gonadal development was investigated in juvenile host fish. The extrapituitaries were collected from mature spermiating fish or from immature fish treated with testosterone. In recipient males and females circulating plasma GtH levels increased following transplantation of both types of pituitaries. Elevated GtH levels presumably triggered steroid synthesis by the immature male gonad since pituitary GtH content was observed to accumulate in recipient males and not in females. However, the potency of the two kinds of pituitaries seemed different since spermatogenesis was stimulated only in some recipient males bearing a mature adult pituitary. This divergence could be due to a different sensitivity to endogenous gonadotropin-releasing hormone (GnRH). Only mature extrapituitaries might be highly sensitive to GnRH, as suggested by results obtained in juvenile host fish after LHRHa treatment. At the end of the 6-week experimental period, this LHRHa treatment stimulated spermatogenesis and induced a significant increase in pituitary GtH content only in juvenile hosts transplanted with a mature pituitary. Such a result was not observed in juvenile hosts submitted to a LHRHa treatment combined or not with the transplantation of juvenile testosterone-treated pituitary. However, previous works have shown that pituitaries collected from immature testosterone-treated fish are sensitive to GnRH. In the present experiment, the amount of GnRH-induced GtH release might have been too low to initiate spermatogenesis during the 6-week experimental period.

Animals↗

Haemodynamic differences in untreated hypertension and hypertension treated with various beta-adrenoceptor antagonists.

1 As a rule, hypertension progresses from an early stage with a high cardiac output (CO) and an inappropriately normal total peripheral resistance (TPR) to later stages with a normal or decreased CO and a high TPR. 2 Low CO and high TPR can be considered detrimental to the blood perfusion in the tissues and organs and thus to their functional and structural integrity. 3 Among beta-adrenoceptor antagonists, some lower blood pressure by reducing CO, thus bringing about a reactive increase in TPR. The result is that, even though blood pressure is reduced, the haemodynamic conditions commanding regional blood flow are qualitatively similar to those in untreated hypertension. To what extent these circumstances may curtail the benefit expected from blood-pressure reduction deserves careful investigation. 4 Pindolol, a beta-adrenoceptor antagonist with an appropriate degree of intrinsic sympathomimetic activity (ISA), lowers blood pressure while lowering TPR and not unduly reducing cardiac performance. These features should on theoretical grounds lead to a greater improvement in the prognosis of hypertension.

Adrenergic beta-Antagonists↗

Hydergine in senile mental impairment.

Among gerontopsychiatric drugs, Hydergine is pharmacologically characterized by agonist action at central dopamine and serotonin receptors. This review presents a summary of the results obtained with Hydergine in numerous controlled trials in patients with senile mental impairment. Assessment was carried out by means of a rating scale (mainly the Sandoz Clinical Assessment Geriatric, or SCAG, scale), psychometric tests (e.g. the Nuremberg Geriatric Inventory, or NGI), and the EEG. Hydergine also lowers serum prolactin, though a correlation with clinical improvement has not been established as yet. In the discussion, the need for objective, measurable and precise indicators in gerontopsychiatry is stressed.

Aged↗