Transplants of 26-day-old rats of an anterior pituitary gland from adult intact or castrated male, 20-day-old or adult ovariectomized female donors (all of which contained large amounts of FSH) resulted in superovulation in recipients on the morning of Day 29. Transplants of the gland from 20-day-old males and adult cyclic females could not advance the time of first ovulation or induce superovulation. In the rats in which superovulation could be induced, a marked increase in plasma FSH was noted in recipients shortly after transplantation and the high levels of plasma FSH were maintained until at least 12 h after grafting. These rats also showed preovulatory surges of LH and FSH 54 h after grafting. No obvious elevation of plasma FSH was noted over 72 h in recipients in which superovulation could not be induced. These findings suggest that the final maturation of follicles for superovulation is induced by a transient release of a large amount of FSH from the grafted pituitary gland and that the sex of the pituitary donor has no bearing on this phenomenon.

Abstract--In order to evaluate the potential usefulness of the drug as an anti depressant, acute and chronic effects of rolipram, a selective inhibitor of Cat' and calmodulin-independent cyclic AMP phosphodiesterase were investigated on muricide in olfactory bulbectomized (OB) rats. Upon single administration to OB rats, rolipram at a dosage of 1 mg/kg body weight suppressed the muricide for 2 hr after its administration.As a consequence of daily administration of rolipram, however, the incidence of muricide at 24 hr after the administration was decreased, and more than 60% of the rats did not exhibit the muricide on the 12th day. After the cessation of the administration, the incidence of the muricide returned to the initial level. The suppression of the muricide was not antagonized by several kinds of neurotransmitter blockers. Administrations of phosphodiesterase inhibitors and dibutyryl cyclic AMP as well as desipramine and clomipramine also suppressed the muricide dose-dependently.Repeated administration of desipramine also gave results similar to those of rolipram: repetition of a short suppression on the muricide was followed by the appearance of a long-lasting suppression.Differently from rolipram and desipramine, dibutyryl cyclic AMP did not cause long-lasting sup pression, and even the direct effect (75% suppression) observed 30 min after its administration on the first day disappeared during its repeated administration for 14 days.From these results, rolipram was considered to show an antidepressant effect through the inhibition of Cat+ and calmodulin-independent cyclic AMP phosphodiesterase.

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ABSTRACT-Terguride, a derivative of the ergot alkaloid, was characterized as a new anti-hyperprolactin emic agent in rats and dogs in comparison with bromocriptine. Terguride was found to bind selectively to the pituitary dopamine D2-receptors with a high affinity (Kd=0.39 nM). In reserpinized rats, terguride at 0.03 mg/kg, p.o. significantly reduced the serum prolactin (PRL) level. The PRL lowering effect and the effective dose were longer lasting and about 30 times lower than those of bromocriptine, respectively. In rats bearing estrogen-induced pituitary prolactinoma, chronic terguride induced shrinkage of the prolactinoma as well as reduction of the high serum PRL level. In lactating rats, terguride (1.0 mg/kg, s.c.) reduced milk production in the mammary gland, whereas bromocriptine showed no significant effect up to 10 mg/kg, s.c. Terguride (10 mg/kg, p.o.) did not induce any stereotypy and hypermotility in reserpinized rats, while bromocriptine induced both stereotypy and hypermotility significantly at 10 mg/kg, p.o. In dogs, terguride, like bromocriptine, reduced the serum PRL level, but did not affect the serum levels of growth hormone and luteinizing hormone. In dogs, bromocriptine induced both emesis and PRL-lowering at almost the same dose, whereas emesis-inducing doses of terguride were about 100 times higher than the PRL-lowering dose. These results suggest that terguride as a dopamine D2-agonist is a potent inhibitor of PRL secretion with less neurotropic side effects compared to bromocriptine, and thus a useful drug for the treatment of galactor rhea and hyperprolactinemia including prolactinoma.Keywords: Terguride, Bromocriptine, Anti-hyperprolactinemic agent, Dopamine D2-agonist, Emetic action Dopamine (DA) D2-agonists, belonging to the family of ergot-derived drugs such as bromocriptine and lisu ride, are well known to be useful for the treatment of disorders characterized by hypersecretion of prolactin (PRL), such as galactorrhea and prolactinoma (1, 2). Bromocriptine, being the most widely utilized, has been shown not only to reduce the high PRL level in patients bearing prolactinoma and in postpartum women, but also to induce shrinkage of the tumor mass and reduction of lactation. However, such treatment is often associated with neurotropic side effects such as nausea and vomiting, which may be due to the D2-agonistic action on the cen tral dopaminergic systems; and as a result, about 10% of the patients discontinued the treatment (3 5). Thus, the drug development in this field recently has been directed to the search for a potent anti-hyperprolactinemic drug without the unwanted neurotropic side effects. Terguride, a 9,10-transdihydrogenated derivative of the ergot alkaloid lisuride, has been reported to exhibit both agonistic and antagonistic pharmacological effects at the DA D2-receptors depending upon the location and the state of the receptors (6-9). Like D2-agonists, terguride inhibits hypersecretion of PRL in reserpinized rats at low doses, suggesting a potent agonistic action on the...

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