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S. K. SAKSENA and R. R. CHAUDHURY

Summary.

One of the aza-analogues, 7,8,9,10-tetrahydro-7-oxo-benzo (c) phenanthridine exhibited an anti-androgenic activity on immature, castrated, male rats. The compound had an interesting anti-androgenic activity as the effect of testosterone-induced gain in weight of the ventral prostate was significantly inhibited by the compound. This compound did not, however, inhibit the androgen-induced weight increase of the seminal vesicle.

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S. K. SAKSENA and R. R. CHAUDHURY

Summary.

Nine azasteroids have been evaluated for antifertility effect in rats when fed orally from Days 1 to 4 of pregnancy at the dose of 10 mg/kg body weight. The compounds 3β-hydroxy-androst-5-ene (16, 17-C)-5-methyl-pyrazole and 1,2,3,4-tetrahydro-N-tosyl-8-methoxy-4-oxo-benzo(b)quinoline inhibited pregnancy at that dose in a significant number of rats.

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B. BARCIKOWSKI, S. K. SAKSENA and A. BARTKE

Prostaglandins (PGs) can be synthesized by the testes (Ellis, 1972) and are present in the male accessory reproductive tissues and in the semen of various mammalian species (Bygdeman, Fredricsson, Svanborg & Samuelsson, 1970; Tan & Privett, 1972). Their physiological rôle in the male reproductive system is not understood but various effects of PG administration on the testes and male reproductive tract have been reported. These include decrease in plasma testosterone levels (Bartke, Musto, Caldwell & Behrman, 1973; Saksena, Safoury & Bartke, 1973), decrease in testicular blood flow (Free & Jaffe, 1972), and effects on contractions of the testis capsule (Seeley, Hargrove, Johnson & Ellis, 1972), on sperm transport (Hunt & Nicholson, 1972), and on contractile responses of the ductus deferens and seminal vesicles in vitro (Stahl, 1972; Taylor & Einhorn, 1972). In the human, certain cases of male infertility appear to be associated with a low seminal content of PGs

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R. R. CHAUDHURY, S. K. SAKSENA and S. K. GARG

Taxus baccata Linn., a tree which grows abundantly in India, has been reported to possess an antifertility effect (Kirtikar & Basu, 1935; Chopra, Nayar & Chopra, 1956; Chopra, Chopra, Handa & Kapoor, 1958; Chaudhury, 1966). Khanna, Garg, Vohora, Walia & Chaudhury (1969) recently reported that anti-implantation activity is present in the leaves. Possible anti-ovulatory activity of different extracts of leaves of Taxus baccata has been screened on fifty-eight, adult, non-pregnant rabbits, each weighing between 1·5 and 2·0 kg. The rabbits were obtained from a local source and housed in independent cages for at least 3 weeks before use. The air-dried, powdered leaves of Taxus baccata were successively extracted with petroleum ether (b.p. 60 to 80° C), alcohol (95 %) and distilled water and the extracts were administered as a suspension with
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S. K. SAKSENA, R. STEELE and M. J. K. HARPER

Summary.

Groups of rats ovariectomized 5 weeks previously were injected daily for 6 days with oestradiol and/or progesterone. Although the dose of oestradiol used was adequate to suppress peripheral serum LH values, none of the treatments significantly altered the peripheral serum levels of prostaglandin F.

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I. F. LAU, S. K. SAKSENA and M. C. CHANG

Evidence has accumulated that insertion of a foreign body into the uterine lumen (Spilman & Duby, 1972; Wilson, Cenedella, Butcher & Inskeep, 1972; Chaudhuri, 1973; Saksena & Harper, 1974; Saksena, Lau & Castracane, 1974) or its distension (Poyser, Horton, Thompson & Los, 1971) induces a significantly greater production of prostaglandin (PG) than in control uteri in several species including man (Batta, Mukerjee & Santhakumari, 1972). Likewise, the elevated levels of PG in the presence of an IUD and its effect on luteal regression (Spilman & Duby, 1972) and the antifertility effect induced by an IUD has been successfully reversed in rabbits by administering indomethacin (Saksena & Harper, 1974), an inhibitor of prostaglandin biosynthesis (Vane, 1971). All this evidence suggests that prostaglandins are involved in the mechanism of action of an IUD. We reported a preimplantation rise of uterine prostaglandin F (PGF) content and concentration in rabbits, rats and hamsters bearing

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S. K. SAKSENA, I. F. LAU and M. C. CHANG

Worcester Foundation for Experimental Biology, Shrewsbury, Massachusetts 01545, and Department of Biology, Boston University, Boston, Massachusetts 02215, U.S.A.

(Received 29th April 1974)

Recent studies implicate prostaglandins (PGs) of the E and F series in the release of anterior pituitary hormones (see Carlson, Barcikowski, & McCracken, 1973). Increases in serum levels of LH (Sato, Taya, Tyujo, Hirono & Igarashi, 1974) FSH and prolactin (Sato, Jyujo, Iesaka, Ishikawa & Igarashi, 1974) were observed following a single injection of PG E1, E2 or F in rats which were spayed and primed with oestrogen plus progesterone. Intrauterine insertion of a Silastic-PVP implant containing PGF has been shown to stimulate the release of LH in rats and hamsters (Saksena, Lau & Chang, 1974). Experiments in which PGs did not affect LH release have also been reported (Chamley & Christie, 1973). Here we report the results of the time sequence of LH

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C. M. LUBICZ-NAWROCKI, S. K. SAKSENA and M. C. CHANG

Prostaglandins are present in the male accessory glands (Goldblatt, 1933; von Euler, 1935; Mann, 1964; Bygdeman, Fredericsson, Svanborg & Samuelsson, 1970), and can be synthesized by rat testis tissue (Ellis, 1972). Studies in sheep (McCracken, 1971; McCracken, Baird & Goding, 1971) indicate that prostaglandins may be the naturally occurring luteolytic factor but the rôle of prostaglandins in male reproductive function has not been determined. Treatment of male rats and mice with prostaglandins E1, E2 and F however, decreases the level of circulating (plasma) testosterone (Bartke, Musto, Caldwell & Behrman, 1973; Saksena, El Safoury & Bartke, 1973). Since mature hamster spermatozoa lose their fertilizing ability within 12 days after castration (Lubicz-Nawrocki & Glover, 1973), it seemed possible that administration of prostaglandins E1 or F (PGE1 or PGF) might induce sterility by lowering the titre of plasma testosterone. The present paper reports on the fertilizing

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I. F. LAU, S. K. SAKSENA and M. C. CHANG

Prostaglandins (PGs) are known to exert profound physiological and pharmacological effects on the female reproductive system in women and in many other species (Weeks, 1972; Labhsetwar, 1974). Indomethacin and aspirin, inhibitors of prostaglandin biosynthesis, block PMSG-induced ovulation in immature (Armstrong & Grinwich, 1972; Orczyk & Behrman, 1972) and adult female rats (Tsafriri, Lindner, Zor & Lamprecht, 1972). In the rabbit, ovulation induced by HCG, LH or coitus was blocked by indomethacin (O'Grady, Caldwell, Auletta & Speroff, 1972). In mice, ovulation was blocked with indomethacin and the effect was reversed by injecting prostaglandins E2 or F (Saksena, Lau & Shaikh, 1974). All these studies provide indirect evidence that PGs are involved in the process of ovulation. A more direct approach, namely the specific binding of endogenous PGs by anti-PG sera raised in rabbits, was used in the present study. Attempts were also made to reverse the antiovulatory effect of

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T. A. Parkening, T. J. Collins, I. F. Lau and S. K. Saksena

Summary. Plasma and pituitary hormones of young (3–5 months of age) dioestrous hamsters with normal cycles and aged (13–17 months of age) anoestrous hamsters were compared. The anoestrous hamsters exhibited lower plasma values of progesterone (P < 0·001), oestradiol-17β (P < 0·005) and prolactin (P < 0·001) and higher levels of plasma gonadotrophins (P < 0·001) than did the dioestrous animals. Pituitary concentrations of LH were higher (P < 0·005) in anoestrous hamsters, but pituitary FSH and prolactin values did not differ. In another series of experiments three groups of hamsters (3–5- and 13–17-month-old with normal cycles and 13–17-month-old in anoestrus) were ovariectomized. Blood samples were taken by cardiac puncture every 3–4 weeks after receiving s.c. injections of oestradiol-17β (1 or 10 μg/100g body wt) for 2 or 9 consecutive days. The markedly lower levels of gonadotrophins in aged anoestrous hamsters indicated that the hypothalamic–hypophysial complex was incapable of responding to the same degree as it did in young and aged cyclic animals. Prolactin values were similarly depressed in all 3 groups. Oestradiol-17β treatment caused reduced gonadotrophin and increasing prolactin concentrations in all 3 groups. These results indicate that the ovaries of the senescent anoestrous hamster produce less steroids and suggest that age-related changes in the hypothalamic–hypophysial complex are largely responsible for the cessation of regular oestrous cycles.