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.

The effects of Methallibure (ICI 33,828) on the LH release in castrate male rats challenged with LHRH.

Daily administration of 10 mg of Methallibure (ICI 33,828) for 6 days to male castrate rats resulted in significant depression of serum radioimmunoassayable luteinizing hormone (LH). Subsequent challenge with 100 ng of synthetic luteinizing hormone-releasing hormone (LHRH) showed these rats to release sufficient pituitary LH to achieve plasma levels equal to those of LHRH treated castrate controls. Although an effect at the level of the pituitary remains to be conclusively ruled out, these results suggest that the predominant in vivo effect of Methallibure in the castrate male rat is to suppress pituitary LH release due to diminished secretion of LHRH by the hypothalamus.

A possible role for oxytocin in sperm transport in the male rabbit.

Administration of methallibure (50 mg/kg body weight, daily) to male rabbits resulted in a 45% reduction in sperm number in ejaculates obtained during the treatment period. Recovery occurred within 48 h after the last dose of methallibure. This decrease in sperm number did not occur when oxytocin (0-2 i.u./kg body weight) was administered simultaneously with methallibure. This suggests that methallibure prevents the release of oxytocin during ejaculation.

Effect of methallibure on gonadotrophic content, ovarian 32P uptake and gonadosomatic index in the freshwater catfish, Heteropneustes fossilis (Bloch).

Gonadotrophin content in the pituitary gland and blood serum as well as ovarian 32P uptake were studied in response to methallibure treatment in H. fossilis. There was a marked reduction in the gonadotrophic activity of the pituitary gland and blood serum within 3 weeks of methallibure treatment (100 microng/g). A simultaneous significant reduction was also recorded in the ovarian activity of these fish. The fall in ovarian activity caused by methallibure could not be prevented by the administration of LH, FSH or LH+FSH. After cessation of methallibure treatment, LH+FSH (50 microng each) administration restored ovarian activity. It is evident from these results that methallibure alters the secretion of gonadotrophin, and also prevents its action on the ovary.

Castration and reproductive behavior in the paradise fish, Macropodus opercularis (L.) (Osteichthyes: Belontiidae).

The effects of castration on male spawning behavior, nestbuilding and fertility were measured in a five day spawning trial with an intact female. Spawning and fertility decreased one week following castration while nestbuilding was unaffected. Sham operated males showed normal spawning and fertility. Two weeks postoperatively, fertility and spawning were increased paralleling partial regeneration of the testes. The antigonadotropin methallibure blocked testes regeneration and recovery of spawning in castrated males but it had no effect on reproductive functions of intact males. Spawning did not decrease in one-week castrated males which were administered testosterone enathanate. The results suggest that gonadal androgen facilitates sexual behavior in Macropodus.

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.

Prolactin content of the pituitary gland in response to hypertonic saline medium, antithyroid drugs, methallibure and thyroxine in a freshwater teleost Heteropneustes fossilis.

Variations in the prolactin content of the pituitary gland in response to different treatments were studied in a freshwater catfish, H. fossilis. One week of saline (1% NaCl medium) treatment reduced the pituitary prolactin content but enhanced the serum prolactin level showing release of prolactin from the pituitary gland. Two weeks of saline treatment reduced pituitary as well as serum prolactin content presumably a result of reduced prolactin synthesis in the pituitary gland. This reduction of synthetic activity in this species is probably due to a drop in prolactin requirement. All the antithyroid durgs tested as well as L-thyroxine decreased the pituitary prolactin content. Methallibure administration induced the release of prolactin from the pituitary as evidenced by the lowered prolactin level in this gland and a simultaneous increase in the prolactin content of the serum.

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.

In vivo change in the germinal vesicle of the sow oocyte during the follicular phase before the ovulatory LH surge.

This study describes a morphological change in the germinal vesicle (GV) of the sow oocyte during the follicular phase preceding the ovulatory LH surge. Estrus synchronization obtained with methallibure treatment provided a reference point for dating the onset of the follicular phase of each sow in the experiment. The oocyte GV's of preovulatory follicles having a diameter of less than 2 mm (during the first 2 to 3 days of the follicular phase) showed uniformly dispersed chromatin with no condensation, while the GV's of oocytes from preovulatory follicles of more than 2 mm diameter (from days 2 and 3 of the follicular phase to day 5) presented condensed chromatin in the shape of a crown or horseshoe surrounding the nucleolus, and irregular chromatin clusters in the nucleoplasm; these clusters were usually found lying against the nuclear membrane.