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R Lachance

Publications and source records attributed to R Lachance.

At least 19 recordsLinked to original sources
PubMed2000

Structure-activity relationships of 17alpha-derivatives of estradiol as inhibitors of steroid sulfatase.

The steroid sulfatase or steryl sulfatase is a microsomal enzyme widely distributed in human tissues that catalyzes the hydrolysis of sulfated 3-hydroxy steroids to the corresponding free active 3-hydroxy steroids. Since androgens and estrogens may be synthesized inside the cancerous cells starting from dehydroepiandrosterone sulfate (DHEAS) and estrone sulfate (E(1)S) available in blood circulation, the use of therapeutic agents that inhibit steroid sulfatase activity may be a rewarding approach to the treatment of androgeno-sensitive and estrogeno-sensitive diseases. In the present study, we report the chemical synthesis and biological evaluation of a new family of steroid sulfatase inhibitors. The inhibitors were designed by adding an alkyl, a phenyl, a benzyl, or a benzyl substituted at position 17alpha of estradiol (E(2)), a C18-steroid, and enzymatic assays were performed using the steroid sulfatase of homogenized JEG-3 cells or transfected in HEK-293 cells. We observed that a hydrophobic substituent induces powerful inhibition of steroid sulfatase while a hydrophilic one was weak. Although a hydrophobic group at the 17alpha-position increased the inhibitory activity, the steric factors contribute to the opposite effect. As exemplified by 17alpha-decyl-E(2) and 17alpha-dodecyl-E(2), a long flexible side chain prevents adequate fitting into the enzyme catalytic site, thus decreasing capacity to inhibit the steroid sulfatase activity. In the alkyl series, the best compromise between hydrophobicity and steric hindrance was obtained with the octyl group (IC(50) = 440 nM), but judicious branching of side chain could improve this further. Benzyl substituted derivatives of estradiol were better inhibitors than alkyl analogues. Among the series of 17alpha-(benzyl substituted)-E(2) derivatives studied, the 3'-bromobenzyl, 4'-tert-butylbenzyl, 4'-butylbenzyl, and 4'-benzyloxybenzyl groups provided the most potent inhibition of steroid sulfatase transformation of E(1)S into E(1) (IC(50) = 24, 28, 25, and 22 nM, respectively). As an example, the tert-butylbenzyl group increases the ability of the E(2) nucleus to inhibit the steroid sulfatase by 3000-fold, and it also inhibits similarly the steroid sulfatase transformations of both natural substrates, E(1)S and DHEAS. Interestingly, the newly reported family of steroid sulfatase inhibitors acts by a reversible mechanism of action that is different from the irreversible mechanism of the known inhibitor estrone sulfamate (EMATE).

Arylsulfatases↗
PubMed1990

Complete response to combination therapy with an LHRH agonist and flutamide in metastatic male breast cancer: a case report.

Twelve months after modified radical mastectomy with axillary dissection (4 out of 13 nodes found positive) in a 66-year old man, bone scintigraphy showed multiple bone metastases. Treatment was started with the combined administration of an LHRH agonist and the pure antiandrogen Flutamide. Six and a half months later, bone scintigraphy was normal while serum testosterone was reduced to 10% of control and the serum concentration of the adrenal steroids was decreased by 23 to 45%. Following relapse of the disease at 12 months, more complete blockade of adrenal steroid secretion was achieved with aminoglutethimide and hydrocortisone. Stability of the disease was then observed up to the last evaluation performed in January 1990 (5 years of stable disease). Since the adrenal steroids are converted into active androgens and estrogens in peripheral tissues, including the breast, the combined therapy has the advantage of reducing the source of potentially active estrogens and androgens while blocking the action of androgens in target tissues. No side-effects other than those due to hypoandrogenicity, namely hot flushes and loss of libido and potency were observed. This well-tolerated treatment achieves complete medical castration, partial medical adrenalectomy, and neutralization of peripheral androgen action.

Aged↗
PubMed1988

Important prognostic value of standardized objective criteria of response in stage D2 prostatic carcinoma.

One hundred and eighty-six previously untreated patients with clinical stage D2 prostate cancer have been followed according to the criteria of objective response of the National Prostatic Cancer Project (NPCP). All patients received combination therapy with the antiandrogen Flutamide and the LHRH agonist (D-Trp6, des-Gly-NH2(10)]LHRH ethylamide (or surgical castration, 10 patients) as first treatment. Forty-nine patients (26.3%) achieved a complete response as best response while 56 (30.1%) and 69 (37.1%) patients had partial and stable responses, respectively, and only 12 patients (6.5%) did not respond to treatment. The median times required to achieve stable, partial and complete responses were 155, 183 and 401 days, respectively. The best response achieved has a major influence on the probability of continuing response and survival. While the 50% probability of continuing response is more than 3 years for the complete responders, it is reduced to 630 and 517 days for partial and stable responders, respectively. While the non-responders have a median life expectancy of 10.0 months, this value is increased to 30.3 and 37.8 months for the stable and partial responders, respectively. The best probability of survival is for the complete responders with a 95.9% probability of survival at 3 years. There is no significant correlation between the time required to achieve a best response (phase 1) and the duration of the response before progression occurs (phase 2) or the time between progression and death (phase 3) for any of the categories of responses. A longer period of time required to achieve a complete response is associated with a longer survival. When analysis is made, in an attempt to predict response, of the baseline characteristics of the patients before treatment, a low number of bone metastases and better performance status are associated with a greater chance of achieving a complete response while partial, stable and progression responses cannot be predicted from the baseline characteristics. The present data show the importance of standardization of the objective criteria of response to treatment in advanced prostate cancer. Thus, the patients who achieve a complete response have a much more favorable prognosis while partial and stable categories of response have a closely similar prognosis which is inferior to the complete responders. Moreover, the present data indicate that the stable category of response has an important prognostic value which is almost superimposable and not statistically different from the partial response in terms of duration of response and survival.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1988

Combination therapy with flutamide and castration (orchiectomy or LHRH agonist): the minimal endocrine therapy in both untreated and previously treated patients with advanced prostate cancer.

One hundred fifty-four patients with clinical stage D2 prostate cancer with no previous endocrine therapy or chemotherapy received the combination therapy with the pure antiandrogen Flutamide and the LHRH agonist [D-Trp]LHRH ethylamide for an average of 22 months (3 to 49). The objective response to the treatment was assessed according to the criteria of the US NPCP. There was a 6.3-fold increase (29.2 versus 4.6%) in the percentage of patients who achieved a complete response as compared to the results achieved in 5 recent studies limited to removal (orchiectomy) or blockade (DES or Leuprolide) of testicular androgens. Only 4.5% of patients did not respond to the combination therapy as compared to an average of 18% by standard therapy. The duration of response is also significantly increased in the patients who received the combination therapy while the death rate was decreased by approximately 2-fold between 2 and 3 years of treatment. The marked (6.3-fold) improvement in the rate of complete objective responses coupled with the 4-fold decrease in the number of non responders, the increased duration of the positive responses and the 2-fold decrease in the death rate at 2 to 3 years of treatment are obtained with the combination therapy using Flutamide and castration with no or minimal secondary effects. In addition, two hundred nine patients with biopsy-proven stage D2 prostatic adenocarcinoma showing disease progression after orchiectomy, DES or an LHRH agonist used alone received the combination therapy with the pure antiandrogen Flutamide. In patients treated with DES, the estrogen was replaced by the LHRH agonist [D-Trp6]LHRH ethylamide. Objective response to therapy was also assessed according to the criteria of the US NPCP. Thirteen patients (6.2%) had a complete response to treatment while partial and stable responses were achieved in 20 (9.6%) and 39 (18.7%) patients, respectively, for a total objective response rate of 34.5%. The mean duration of response was 24 months. While, in the non responders, the median survival was 8.13 months with a 17% probability of survival at 2 years, the probability of survival of patients who showed partial and stable responses at 2 years was 87 and 67%, respectively. All patients who achieved a complete response are still alive. Considering the excellent tolerance coupled with an objective response observed in 34.5% of the patients, the combination therapy with Flutamide and castration (surgical or LHRH agonist) appears to be the treatment of choice for prostate cancer patients in relapse after standard endocrine therapy.

Adenocarcinoma↗
PubMed1987

Combination therapy with flutamide and castration (orchiectomy or LHRH agonist): the minimal endocrine therapy in both untreated and previously treated patients.

Patients (154) with clinical stage D2 prostate cancer with no previous endocrine therapy or chemotherapy received the combination therapy with the pure antiandrogen Flutamide and the LHRH agonist [D-Trp6]LHRH ethylamide for an average of 22 months (3-49 months). The objective response to the treatment was assessed according to the criteria of the US NPCP. There was a 6.3-fold increase (29.2 vs 4.6%) in the percentage of patients who achieved a complete response as compared to the results achieved in five recent studies limited to removal (orchiectomy) or blockade (DES or Leuprolide) of testicular androgens. Only 4.5% of patients did not respond to the combination therapy as compared to an average of 18% by standard therapy. The duration of response is also significantly increased in the patients who received the combination therapy. The death rate was decreased by approximately 2-fold between 2 and 3 yr of treatment. The marked (6.3-fold) improvement in the rate of complete objective responses coupled with the 4-fold decrease in the number of non-responders, the increased duration of the positive responses and the 2-fold decrease in the death rate at 2-3 yr of treatment are obtained with the combination therapy using Flutamide and castration with no or minimal secondary effects.

Adenocarcinoma↗
PubMed1987

Flutamide eliminates the risk of disease flare in prostatic cancer patients treated with a luteinizing hormone-releasing hormone agonist.

Although chronic treatment with luteinizing hormone-releasing hormone agonists achieves castration levels without side effects other than those related to hypoandrogenism, a limitation to their use alone for the treatment of prostatic cancer is the transient increase in serum androgens that lasts for 5 to 8 days at the start of treatment with the risk of disease flare. Our data show that the concomitant administration of the pure antiandrogen flutamide in association with the luteinizing hormone-releasing hormone agonist (D-Trp6) luteinizing hormone-releasing hormone ethylamide caused a 64 to 78 per cent decrease in serum prostatic acid phosphatase on days 3 and 7 after the start of treatment in 70 patients with previously untreated stage D2 prostatic cancer. Pain, which was present in 41 patients at the start of treatment, did not increase in any patient, it decreased in 7 at 1 week and it disappeared or decreased in 27 at 2 weeks. Performance, which originally was abnormal in 34 patients, became normal in 7 within 1 week and in 20 within 1 month (59 per cent). These data show that the addition of flutamide completely eliminates the risks of disease flare associated with the use of the otherwise exceptionally well tolerated luteinizing hormone-releasing hormone agonists in patients treated for prostatic cancer.

Acid Phosphatase↗
PubMed1987

Characteristics of radioimmunoassays for the alpha- and beta-subunits of human luteinizing hormone.

The binding characteristics and specificities of the National Hormone and Pituitary Program (NHPP) kits for the radioimmunoassay of the alpha- and beta-subunits of human luteinizing hormone (hLH-alpha and hLH-beta) were studied, as well as the specificities of the anti-hLH and anti-human follicle stimulating hormone (anti-hFSH) antisera distributed by the same organization. The affinity constants of the anti-hLH-alpha and anti-hLH-beta antisera were calculated at 157 +/- 8.4 nM-1 and 109 +/- 7.4 nM-1, respectively. Both antisera were highly specific with regard to the other subunit. However, in the homologous hLH-alpha RIA, native hLH cross-reacted at 21.9%, hFSH at 17.5% and hTSH at 7.9%. The alpha-subunit of the human chorionic gonadotropin, hCG-alpha, was equipotent with the hLH-alpha standard in this assay. In the homologous hLH-beta RIA, hLH showed a cross-reactivity of 14.7% while the cross-reactivities of hCG-beta, hFSH and hTSH were 3.5%, 1.2% and 0.6%, respectively. The anti-hFSH antiserum was highly specific, while the anti-hLH antiserum showed non parallel competition curves. With this knowledge of the specificity of each antiserum, corrections can be properly made for the assays of hLH, hLH-alpha and hLH-beta while the hFSH RIA can be used without correction for the presence of the three other components.

Antibody Specificity↗
PubMed1986

Loss of luteinizing hormone bioactivity in patients with prostatic cancer treated with an LHRH agonist and a pure antiandrogen.

Chronic treatment of adult men with LHRH agonists causes a decrease in serum testosterone and 5 alpha-dihydrotestosterone to castrate levels. In the presence of such low levels of circulating testicular androgens, the concentration of serum LH measured by radioimmunoassay (RIA) sometimes remains normal or is only partially inhibited. In order to assess the biological activity of circulating LH, we have used the mouse interstitial cell assay. Blood samples were obtained from patients with prostatic carcinoma treated with the LHRH agonist [D-Trp6] LHRH ethylamide in combination with the pure antiandrogen Flutamide (Euflex). While serum LH levels measured by RIA were only partially reduced from 2.2 +/- 0.3 (SEM) to 1.1 +/- 0.1 ng/ml after 3 months of therapy, bioactive LH was markedly inhibited from 0.43 +/- 0.04 to 0.030 +/- 0.007 ng/ml, thus causing the ratio of biologically active to radioimmunoassayable LH to drop from 0.26 +/- 0.03 to 0.03 +/- 0.01. In the same patients, serum testosterone levels were decreased from 3.91 +/- 0.51 to 0.14 +/- 0.05 ng/ml after 3 months of treatment. In patients treated for 6 months, the bio/immuno ratio was still reduced at 0.032 +/- 0.005. These data show a marked loss of LH biological activity during treatment of adult men with an LHRH agonist and an antiandrogen. The close parallelism observed between serum testosterone and bioactive LH levels suggests that the loss of biological activity of the gonadotrophin is mainly, if not exclusively, responsible for the inhibition of testicular androgen secretion observed during chronic treatment with LHRH agonists.

Adenocarcinoma↗
PubMed1986

Serum luteinizing hormone (LH) biological activity in castrated patients with cancer of the prostate receiving a pure antiandrogen and in estrogen-pretreated patients treated with an LH-releasing hormone agonist and antiandrogen.

We recently reported almost complete disappearance of serum LH biological activity in previously untreated patients with advanced prostatic cancer receiving combined therapy with a LHRH agonist and a pure antiandrogen. This decrease in LH bioactivity was most likely responsible for the fall of circulating testosterone to castration levels during such treatment. Since patients previously treated with high doses of estrogens or orchiectomy before receiving combined therapy had a less favorable response to the new treatment, we measured serum LH levels by RIA and the mouse interstitial cell bioassay in these 2 groups of patients. Serum samples were obtained from 14 men with advanced prostatic cancer treated from 9-41 months (24 +/- 9 months) with diethylstilbestrol before receiving 500 micrograms/day LHRH agonist ([D-Trp6]LH/RH ethylamide) in combination with 3 daily oral doses of 250 mg pure antiandrogen flutamide and from 21 men castrated for at least 9 months (32 +/- 26 months) before receiving the antiandrogen alone. In previously castrated patients, both bio- and immunoactive LH serum levels were elevated and did not change during at least 3 months of antiandrogen treatment. In estrogen-pretreated men, however, bioactive LH concentrations declined from 1.2 +/- 0.5 (+/- SEM) to 0.04 +/- 0.01 ng/ml after 1 month of combined treatment and remained low thereafter, while serum LH levels, measured by RIA, did not significantly decline (1.4 +/- 0.5 vs. 0.9 +/- 0.1 ng/ml on days--2 and 30, respectively). This decrease in LH biopotency caused the biological to immunological activity ratio to fall from 0.5 +/- 0.2 before the onset of the combined therapy to 0.05 +/- 0.01 after 3 months. Thus, estrogen pretreatment did not prevent the ability of the LHRH agonist-antiandrogen combination to decrease serum LH biological activity. Moreover, the absence of an effect in castrated patients receiving antiandrogen alone indicates that the LHRH agonist, and not flutamide, was responsible for the effects of the combined therapy.

Aged↗
PubMed1986

Stimulation of the circulating levels of glycoprotein hormone alpha-subunit after combined administration of a luteinizing hormone-releasing hormone (LHRH) agonist and flutamide in patients with cancer of the prostate.

To ascertain whether the immunoreactive luteinizing hormone (LH) levels measured following the combined treatment may represent cross-reaction of the LH antiserum with LH subunits, we have examined the effects of therapy on the serum levels of free alpha- and free LH-beta-subunits in intact, castrated, and estrogen-treated patients. In previously untreated patients receiving the LHRH agonist [D-Trp6,des-Gly-NH2(10)]LHRH ethylamide in association with the pure antiandrogen Flutamide, serum-free alpha-subunit levels were stimulated from 0.09 +/- 0.02 to 3.10 +/- 0.84 ng/ml after 5 days, and declined slowly afterwards to 1.33 +/- 0.20 ng/ml after 3 months of combined treatment. In patients pretreated from 12 to 24 months (17.5 +/- 1.0 months) with diethylstilbestrol (DES) prior to receiving the combined therapy, free serum alpha-subunit concentration followed a similar pattern, rising from 0.22 +/- 0.03 to 1.78 +/- 0.28 ng/ml after 15 days of combined treatment, and declining thereafter to 0.81 +/- 0.10 ng/ml after 3 months. Free LH-beta-subunits were below the detection limit in most previously untreated patients and in all DES-treated patients. After correcting for the cross-reactivity of the alpha-subunit in the LH RIA, immunoassayable LH serum levels in previously untreated patients were only slightly reduced from 0.81 +/- 0.06 ng/ml before the onset of the combined treatment to 0.52 +/- 0.05 ng/ml after 3 months. On the contrary, bioactive serum LH levels were drastically inhibited from 0.43 +/- 0.04 to 0.03 +/- 0.01 ng/ml after the same duration of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Androgen Antagonists↗
PubMed1985

Long term treatment with luteinising hormone releasing hormone agonists and maintenance of serum testosterone to castration concentrations.

Serum concentrations of luteinising hormone and testosterone were measured by radioimmunoassay one, two, four, seven, and 24 hours after the subcutaneous administration of 500 micrograms of the luteinising hormone releasing hormone agonist [D-Trp6, des-Gly-NH2(10)] LHRH ethylamide or [D-Ser(TBU)6, des-Gly-NH2(10)]LHRH ethylamide in patients who had previously received daily treatment with these peptides for 0, 1, 6, 12, 18, and 24 months. No increase in the serum concentrations of luteinising hormone or testosterone were detected at any time between one and 24 months' treatment. The data show that daily subcutaneous administration of the two luteinising hormone releasing hormone agonists used at the appropriate dose can maintain concentrations of serum androgens equivalent to those after castration during long term treatment.

Bone Neoplasms↗
PubMed1985

Defining the information content of health data systems.

Uses of health information systems depend heavily on the background and experiences of those who evaluate the data. Effective collaboration between physicians and system managers can enhance significantly the decision-making and information obtained from these systems. This article describes some methods of collaboration and the current uses of one system developed through collaborative efforts of physicians and system managers.

Ambulatory Care↗
PubMed1984

Modulation of cyclic AMP formation and progesterone secretion by human chorionic gonadotropin, epinephrine, buserelin and prostaglandins in normal or human chorionic gonadotropin desensitized rat immature luteal cells in monolayer culture.

It is now well recognized that hCG-induced luteolysis is associated with hCG-induced desensitization, but the physiological significance of luteal cell GnRH, PGS and beta-receptors is still undefined. Therefore, we intend in this study to observe the effects of prostaglandin F2 alpha and prostaglandin E2 and the interactions between epinephrine, a potent LHRH agonist [(D-Ser-(TBu)6, des-Gly-NH2(10)) LHRH ethylamide: Buserelin] and hCG in normal and in vitro hCG-desensitized rat immature luteal cells in monolayer culture, on basal, hCG or cholera toxin stimulated intracellular and extracellular cyclic AMP and progesterone secretion. The present report shows that incubation of immature rat luteal cells in monolayer culture with Buserelin, led to 25-50% inhibition of the epinephrine--as well as PGE2--induced cyclic AMP and progesterone responses. The LHRH agonist can also reverse the stimulatory effects of cholera toxin in the presence of hCG and led with PGF2 alpha, to additive inhibitory effects on extracellular cyclic AMP accumulation induced by cholera toxin. Both Buserelin and PGF2 alpha can reverse the hCG-induced cyclic AMP and progesterone release but no effect could be observed when the incubation was carried out with either substance in the absence of hCG. Prostaglandin E2, in acute conditions of incubation, seems to share agonist properties with hCG when both were incubated with luteal cells. Buserelin reversed the stimulatory effects of PGE2, hCG, epinephrine, and cholera toxin on cyclic AMP and progesterone responses to these substances. These results suggest that Buserelin and PGF2 alpha have luteolytic-like effects and that there may be a complementary action for the two substances. Preincubation of rat luteal cells in monolayer culture with 1 nM hCG for a 24 h period led to the inhibition of cyclic AMP and progesterone responses after a subsequent exposure to hCG and epinephrine. Luteal cells were no longer responsive to hCG while the presence of epinephrine in hCG-desensitized cells led to a 40% stimulation of cAMP and progesterone production. These observations suggest that there occurred a partial alteration of the N component activity of the adenylyl cyclase system.

Animals↗
PubMed1984

Modulation of cyclic AMP formation and progesterone secretion by human chorionic gonadotropin, epinephrine, buserelin and prostaglandins in normal or human chorionic gonadotropin desensitized rat immature luteal cells in monolayer culture.

It is now well recognized that hCG-induced luteolysis is associated with hCG-induced desensitization, but the physiological significance of luteal cell GnRH, PGs and beta-receptors is still undefined. Therefore, we intend in this study to observe the effects of prostaglandin F2 alpha and prostaglandin E2 and the interactions between epinephrine, a potent LHRH agonist [(D-Ser-(TBu)6, des-Gly-NH10(2) LHRH ethylamide: Buserelin] and hCG in normal and in vitro hCG-desensitized rat immature luteal cells in monolayer culture, on basal, hCG or cholera toxin stimulated intracellular and extracellular cAMP and progesterone secretion. The present report shows that incubation of immature rat luteal cells in monolayer culture with Buserelin, led to 25-50% inhibition of the epinephrine-as well as PGE2-induced cAMP and progesterone responses. The LHRH agonist can also reverse the stimulatory effects of cholera toxin in the presence of hCG and led with PGF2 alpha, to additive inhibitory effects on extracellular cAMP accumulation induced by cholera toxin. Both Buserelin and PGF2 alpha can reverse the hCG-induced cAMP and progesterone release but no effect could be observed when the incubation was carried out with either substance in the absence of hCG. Prostaglandin E2, in acute conditions of incubation, seems to share agonist properties with hCG when both were incubated with luteal cells. Buserelin reversed the stimulatory effects of PGE2, hCG, epinephrine and cholera toxin on cAMP and progesterone responses to these substances. These results suggest that Buserelin and PGF2 alpha have luteolytic-like effects and that there may be a complementary action for the two substances. Preincubation of rat luteal cells in monolayer culture with 1 nM hCG for a 24 h period led to the inhibition of cAMP and progesterone responses after a subsequent exposure to hCG and epinephrine. Luteal cells were no longer responsive to hCG while the presence of epinephrine in hCG-desensitized cells led to a 40% stimulation of cAMP and progesterone production. These observations suggest that occurred a partial alteration of the N component activity of the adenylyl cyclase system.

Animals↗
PubMed1982

Effect of GnRH-induced endogenous luteinizing hormone release and exogenous progestogen treatment on ovarian activity in the postpartum ewe.

In two experiments, 64 crossbred ewes that had lambed in September or January and had their lambs removed within 24 h after birth were assigned to four groups and given the following treatments: group 1 (16 ewes)-1 ml saline, im or iv on d 10 postpartum; group 2 (24 ewes)-150 microgram/gonadotropin releasing hormone (GnRH) in 1 ml saline, im or iv on d 10 postpartum; group 3 (16 ewes)-150 microgram/GnRH in 1 ml saline, im or iv on d 10 postpartum, plus 40 mg fluorogestone acetate (FGA)-impregnated intravaginal sponges for 12 d beginning 22 d postpartum and group 4 (eight ewes)-40 mg FGA-impregnated intravaginal sponges only for 12 d beginning 22 d postpartum. Pregnant mare's serum gonadotropin (500 IU) was injected im into FGA-treated ewes at the time of sponge removal. Blood samples were collected from eight ewes in groups 1 and 2 at regular intervals up to 2 and 6 h, respectively, after treatment and analysed for luteinizing hormone (LH). Plasma progesterone (P) levels in blood collected once or twice weekly were used to monitor ovarian activity. GnRH induced a release of LH in all ewes monitored, whereas the LH levels remained unchanged in saline-treated ewes. Only 44% of the latter ewes had shown evidence of luteal activity by 50 d postpartum. The mean plasma P levels in the GnRH-treated ewes did not rise above basal preinjection values during the 14 d after treatment. In contrast, a synchronized ovulation followed by normal luteal activity was induced in 88% of the FGA-sponge-treated ewes. Of 16 ewes from group 2 slaughtered 26 d postpartum, 13 had ovaries that contained luteinized structures and uterine involution was incomplete in six ewes. These results preclude the use of GnRH as a single injection for induction of cyclic ovarian activity in the early postpartum ewe and indicate the need for progestogen treatment to initiate cyclic ovarian activity by 35 d postpartum. However, incomplete uterine involution may limit the number of ewes that can be successfully rebred at this time.

Animals↗
PubMed1976

Characteristics of the interaction between thyrotropin-releasing hormone and somatostatin for thyrotropin and prolactin release.

Somatostatin, at concentrations up to 10(-7) M, does not inhibit the basal release of TSH from primary cultures of rat anterior pituitary cells. The TRH-induced TSH release is however 65% reduced by somatostatin, half-maximal inhibition being measured at 2.5 x 10(-10) M somatostatin. The concentration of TRH giving half-maximal stimulation (ED50) of TSH release is only slightly increased from 1 to 3 x 10(-9) M in the presence of 10(-8) M somatostatin. Somatostatin inhibits by 45-65% both the basal and TRH-induced PRL release of pituitary cells prepared from adult female rats, with half-maximal inhibition at approximately 5 x 10(-10) M somatostatin. The TRH ED50 for PRL release was not significantly affected by somatostatin. Somatostatin (200 mug) has no effect on the basal plasma levels of TSH or PRL in anesthetized male rats treated with estradiol benzoate (EB), hypothyroid rats, or hypothyroid animals treated with EB. The plasma TSH response to TRH is, however, reduced by approximately 75% by somatostatin while the plasma PRL response is not affected by injection of the peptide. The interaction between TRH and somatostatin for both TSH and PRL release is non-competitive and is thus likely to occur at a step subsequent to the binding of the peptides to their specific receptors in both thyrotrophs and mammotrophs.

Animals↗