Methallibure inhibition of testicular and seminal vesicle activity in catfish, Clarias batrachus (Linn.): a study correlating changes in serum sex steroid profiles.

The administration of methallibure (2 microg/g BW, daily for 15 days) in Clarias batrachus in prespawning phase (May-June) resulted in decreased weights of seminal vesicle (SV) and testis, and reductions in the concentrations of total proteins, fructose, hexosamines, and sialic acid in SV and testis. The inhibitory changes can be attributed to impairment of steroidogenesis, serum levels of testosterone and estradiol -17beta decreased significantly. Withdrawal of methallibure treatment for 7 and 15 days resulted in gradual recovery and restoration of all the above parameters except the sialic acid levels in the SV and testis, and fructose level in the SV. The methallibure induced regressive changes in the SV and testis were discussed in the light of its GTH inhibiting property.

Compensation by pulsatile GnRH infusions for incompetence for oestradiol-induced LH surges in long-term ovariectomized gilts and castrated male pigs.

The aim of this study was to investigate incompetence for oestradiol-induced LH surges in long-term ovariectomized gilts and male pigs. Gilts (250 days old; n = 36), which had been ovariectomized 30 (OVX 30) or 100 days (OVX 100) before the start of treatment, were challenged i.m. with oestradiol benzoate and were either given no further treatment, fed methallibure to inhibit endogenous GnRH release or fed methallibure and given i.v. pulses of 100 or 200 ng GnRH agonist at 1 h intervals during the LH surge (48-96 h after oestradiol benzoate). The same treatments were applied to long-term orchidectomized male pigs (ORC, n = 23). In addition, one ORC group was not injected with oestradiol benzoate but was fed methallibure and given pulses of 200 ng GnRH agonist. Oestradiol benzoate alone induced an LH surge in the OVX 30 group only (5/6 gilts), methallibure suppressed (P < 0.05) oestradiol benzoate-induced LH secretion, while pulses of 100 ng GnRH agonist in animals fed methallibure produced LH surges in four of six OVX 30 and four of six OVX 100 gilts. The induced LH surges were similar to those produced by oestradiol benzoate alone in OVX 30 gilts. Pulses of 200 ng GnRH agonist produced LH surges in OVX 30 (6/6) and OVX 100 (6/6) gilts and increased the magnitude of the induced LH surge in OVX 100 gilts (P < 0.05 compared with 100 ng GnRH agonist or OVX 30 control). Pulses of 200 ng GnRH agonist also induced LH surge release in ORC male pigs (5/6), but were unable to increase LH concentrations in a surge-like manner in ORC animals that had not been given oestradiol benzoate, indicating that oestradiol increases pituitary responsiveness to GnRH. These results support the hypothesis that oestradiol must inhibit secretion of LH before an LH surge can occur. It is concluded that incompetence for oestradiol-induced LH surges in long-term ovarian secretion-deprived gilts and in male pigs is due to the failure of oestradiol to promote a sufficient increase in the release of GnRH.

Biogenic amines in the hypothalamus of rats after diethyldithiocarbamate or AIMAX treatment, an alternative for norepinephrine depletion.

The objective of this study was to determine whether AIMAX (a dithiocarbamoylhydrazine derivative) is suitable for determining the effects of norepinephrine (NE) depletion on reproduction in domestic animals. Therefore, the effect of AIMAX (n = 6) on concentrations of biogenic amines in the medial basal hypothalamus (MBH) and anterior hypothalamic area (AHA) of ovariectomized (OVX) rats primed with ovarian steroids was compared to that of diethyldithiocarbamate (DDC; n = 5), a potent dopamine-beta-hydroxylase (DBH) inhibitor, which is chemically similar to AIMAX. Rats that received only ovarian steroids and saline injections served as controls (n = 6). Treatment with DDC resulted in sedation and reduced body temperature. In contrast, rats behaved normally after AIMAX treatment. AI-MAX reduced (P < .05) NE but increased (P < .05) dopamine (DA) concentrations in MBH and AHA compared with controls. Similar changes in NE and DA concentrations were observed in DDC-treated rats. However, elevated epinephrine (EPI) levels were measured in MBH and AHA of only DDC-treated rats. Serum LH concentrations were suppressed (P < .005) in both AIMAX- and DDC-treated rats compared with control animals. Because AIMAX, like DDC, suppressed hypothalamic NE content and LH secretion, AIMAX should be useful in studying effects of NE depletion on gonadotropin secretion in domestic animals.

Involvement of the central noradrenergic system in opioid modulation of luteinizing hormone and prolactin secretion in the pig.

The role of norepinephrine (NE) in the progesterone (P)-dependent endogenous opioid peptide (EOP) suppression of LH and prolactin (PRL) secretion in the pig was studied. Fifteen ovariectomized gilts treated with P (0.85 mg/kg b.w. i.m.) twice daily for 10 days were assigned, 5 gilts each, to the following treatment groups: 1) control, 2) AIMAX (N-methyl-N1[1-methyl-2-propenyl]1,2 hydrazinedicarbothioamide), and 3) anti-GnRH serum. On day 4 of P treatment, AIMAX (125 mg per 1.8 kg feed/day), previously shown to be an NE synthesis inhibitor, was fed daily for 7 days to group 2. On the last day of P treatment, group 3 gilts received an i.v. injection of anti-GnRH serum at 0800 h while Group 1 animals received an i.v. injection of serum collected from hypophysectomized gilts. Jugular blood samples were collected every 15 min for 9 h starting at 1000 h. All gilts received two injections of naloxone (NAL; 1 mg/kg b.w., i.v.) at 1400 h and 1600 h and an injection of a GnRH analogue (D-[Ala6-desGly-NH10]-ethylamide; 5 micrograms/pig, i.v.) at 1800 h. Pretreatment serum LH concentrations were lower (p < 0.05) in AIMAX-treated gilts (0.19 +/- 0.09 ng/ml) than in controls (0.53 +/- 0.09 ng/ml), but were similar to those in GnRH antiserum-treated gilts (0.32 +/- 0.09 ng/ml). NAL increased (p < 0.001) serum LH concentrations in control animals and averaged 1.6 +/- 0.2 ng/ml the first h. AIMAX and anti-GnRH serum blocked the NAL-induced LH secretion. Serum PRL concentrations averaged 6.0 +/- 0.1 ng/ml for all groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Serotonin levels in the hen ovarian follicles after methallibure (I.C.I 33, 828) treatment.

The purpose of the present study was to examine the effect of methallibure (MLB), a non-steroid inhibitor of pituitary gonadotrophic activity on serotonin (5-HT) levels in the wall of preovulatory follicles (F1-F4) in the domestic hen. 5-HT was determined spectrofluorometrically. Hens were treated with MLB (10 mg/hen per os) twice a day for 3 successive days. 5-HT was determined in F1-F4 (F1 greater than F2 greater than F3 greater than F4) follicles of the control group, on the next day (MLB-1 group) and 6 days following cessation of MLB administration (MLB-6 group). During MLB treatment egg production was inhibited in all hens. In the MLB-6 group, five hens out of seven took up egg laying on the sixth day after MLB administration. Within each examined group there were no significant differences in 5-HT concentration between F1-F4 follicles. In comparison to the control, MLB caused a significant (P less than 0.01-0.05) increase of 5-HT concentration in F1 (MLB-1 group) and F4 (both MLB-groups). The results obtained indicate that there is a relationship between pituitary activity and 5-HT levels in the preovulatory follicles of the domestic hen.

[The fertility performance (litter characteristics) of laboratory mice over 6 generations after the administration of zinc metallibure as suisynchronous premix and cloprostenol as estrophane]. / Untersuchungen zu Fruchtbarkeitsleistungen (Wurfmerkmale) von Labormäusen im Verlaufe von 6 Generationen nach Verabreichung von Zink-Metallibur als Suisynchron-Prämix und Cloprostenol als Oestrophan.

Suisynchron premix and oestrophane were tested through 6 generations of laboratory mice for their action on fertility (litter parameters). No fertility-reducing effect was recordable.

Absence of an estradiol-induced surge of luteinizing hormone in pigs receiving unvarying pulsatile gonadotropin-releasing hormone stimulation.

The goal of this study was to pharmacologically block central nervous system (CNS) input to gonadotropes in mature ovariectomized gilts to determine the direct actions of estradiol (E2) on pituitary LH release when given at a dose sufficient to elicit a gonadotropin surge. Feeding AIMAX [N-methyl-N'-(1-methyl-2-propenyl)1,2-hydrazinedicarbothioamide; 125 mg/day] for 7 days reduced serum LH concentrations from 1.25 +/- 0.13 (mean +/- SE) to less than 0.18 ng/ml, abolished LH pulses, but did not compromise LH release in response to exogenous GnRH. Serum FSH concentrations were reduced by 27%, whereas serum concentrations of PRL, GH, thyroid hormones and cortisol were not affected after 7 days of AIMAX treatment. Behavior was not altered, aside from a slightly reduced appetite. The LH surge that peaked 48-80 h after injecting E2 benzoate (E2B) into control gilts was blocked in five of eight gilts given AIMAX. Giving GnRH pulses (1 microgram every 45 min) to AIMAX-treated gilts restored mean serum LH concentrations as well as the frequency and amplitude of LH pulses to those of untreated ovariectomized gilts. E2B suppressed the LH response to these GnRH pulses by 88% at 12 h, whereas from 24-96 h after E2B treatment, the LH response to GnRH and mean serum concentrations of LH were again similar to those of controls not given estradiol. These data indicate that induction of the gonadotropin surge by E2 in the gilt requires CNS input. The action of E2 on the pituitary in the presence of unvarying GnRH pulsation may, however, be limited to an early transient inhibition of responsiveness to GnRH, with no subsequent direct stimulation during the period of the surge.

Effect of methallibure on gestation in the guppy, Poecilia reticulata.

Methallibure treatment (1 mg fed on alternate days to a female and a male kept in 1 liter of 25% seawater) started from 1 or 7 days postpartum (early gestation) inhibited gestation in the wild guppy, Poecilia reticulata. A few of the fish treated from 7 days postpartum (2/9) did give birth, but the young either were dead at birth or did not survive long after birth. When treatment was started 2 weeks postpartum (midgestation), gestation was not inhibited, but 25% of the young were born dead while the rest showed retardation of postnatal growth. Several possible interpretations of the results are discussed.

Control of time of parturition in pigs.

Injection of prostaglandin (PG) F-2 alpha or its analogues has provided a technique to induce parturition after Day 110 of gestation in the sow. The mean interval from PG injection to parturition ranges from 24 to 28 h, but only 50-60% of the sows farrow during an 8-10 h working day, and as many as 20% of sows may begin parturition before the injection of PG or less than 22 h after the injection. The duration of parturition is positively associated with the incidence of stillbirths and perinatal death so that techniques to reduce the duration of parturition may save piglets. Early parturition has been prevented by feeding sows progestagens, PG synthesis inhibitors and hypothalamic function inhibitors. These compounds were detrimental to piglet survival if they delayed parturition too long after the expected time of parturition. Parturition was delayed in sows up to 1.5 days by altrenogest, 1.6 days by meclofenamic acid, 2.7 days by indomethacin, and 3 days by methallibure without increased incidence of stillborn piglets compared with control sows. Injection of PG after administration of altrenogest or meclofenamic acid was successful in experiments with sows; parturition could be confined to a 5-day working week with no increase in stillborn piglets compared with control sows. Relaxin injected at 48 and 24 h before or only 24 h before injection of PG increased the proportion of sows farrowing 22-32 h after PG to 86.2% compared with sows injected only with PG (53.3%, P less than 0.01). Oxytocin injected 20 h after injection of PG increased the proportion of sows farrowing 20-28 h after PG to 90.4% compared with sows injected only with PG (49.2%, P less than 0.005). Injection of 25-60 i.u. ACTH on Day 110 of gestation did not shorten the length of gestation, but did decrease the incidence of still born piglets by 0.2 piglets/litter (P less than 0.05). An injection of the beta-adrenergic antagonist, carazolol, during labour before the birth of the first piglet decreased the duration of parturition and the incidence of stillborn piglets particularly in primiparous sows (P less than 0.05). Carazolol injected with oxytocin 20 h after injection of PG decreased the interval from PG to parturition by 2 h compared with sows injected with only PG and oxytocin.(ABSTRACT TRUNCATED AT 400 WORDS)

[Selection of laboratory rats for fertility components in synchronized estrus using Suisychron-Praemix. 1. Effects of selection and synchronization]. / Selektion auf Komponenten der Fruchtbarkeit bei der Laboratoriumsratte unter den Bedingungen der Brunstsynchronisation mit Suisynchron-Prämix. 1. Mitteilung: Wirkung von Selektion und Synchronisation.

The following results were obtained from experimental studies into effects of selection for fertility and into synchronised oestrus though eight generations of laboratory rats: -- The result of selection recordable from the population with selection only was better than that recorded from the population with selection and synchronised oestrus. This has been attributed to higher correlation between phenotype and genotype in the selection variant. -- Direct negative impact of synchronised oestrus on selection index was recorded from a population with random mating. -- The effects of synchronised oestrus regarding selection success were offset but not entirely ruled out by selection. -- Through the generations of both populations with synchronised oestrus the effects of synchronisation were lowered due to both physiological adaptation to Suisynchron application and contraselection with regard to suitability for synchronisation.

[Selection of laboratory rats for fertility components in synchronized estrus using Suisynchron-Praemix. 2. Results of litter development]. / Selektion auf Komponenten der Fruchtbarkeit bei der Laboratoriumsratte unter den Bedingungen der Brunstsynchronisation mit Suisynchron-Prämix. 2. Mitteilung: Ergebnisse der Wurfentwicklung.

The following results were obtained from experimental studies into selection of laboratory rats for fertility and random mating with oestrus being synchronised by means of Suisynchron-Prämix, through eight generations: --Success of selection without synchronised oestrus was higher than that with synchronised oestrus by selection according to the basic index and with one and the same selection intensity. --Litter size and weight were higher in the selected variants, as a result of increased potential fertility (rate of ovulation). --In the population with selection and synchronised oestrus a negative relationship was found to exist between the directly correlated selection results regarding fertility parameters, on the one hand, and the effect of synchronisation, on the other. --Both the rates of ovulation and litter parameters were lower in the population with selection and synchronised oestrus, as a result of synchronisation. --The effect of synchronised oestrus on the population with selection and synchronised oestrus was partially eliminated owing to selection for fertility.

The effect of methallibure (I.C.I., 33828) on the ovary of the carp, Cyprinus carpio.

A study has been made on the effect of methallibure (I.C.I., 33828) on ;the ovary of Carp. C. carpio. Methallibure treatment may exert marked inhibitory influence on vitellogenesis in the fish and cause atresia of vitellogenic follicles, the oogonial proliferation is stepped up. The site and mode of action of methallibure is discussed.