Yun-Yen Tsong
Population Council
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Featured researches published by Yun-Yen Tsong.
Steroids | 2000
Narender Kumar; Shohei Koide; Yun-Yen Tsong; Kalyan Sundaram
Nestorone(R) (Nestorone 16-methylene-17alpha-acetoxy-19-norpregn-4-ene-3,20-dione), formerly referred to as ST 1435, is a potent progestin when given parenterally via sustained release formulations. The pharmacological profile of Nestorone was compared with that of levonorgestrel and 3-keto-desogestrel by steroid receptor binding studies and by in vivo bioassays in rats and rabbits. 3-Keto-desogestrel showed the highest binding affinity to progesterone receptors (PR) followed by Nestorone, levonorgestrel, and progesterone. The binding affinity of Nestorone to androgen receptors (AR) was 500- to 600-fold less than that of testosterone. However, both levonorgestrel and 3-keto-desogestrel showed significant binding (40 to 70% of testosterone) to AR. None of the progestins bound to estrogen receptors (ER). The progestational activity of Nestorone, levonorgestrel, and progesterone was compared using McPhail index in immature rabbits and pregnancy maintenance and ovulation inhibition tests in rats after subcutaneous (s.c.) administration. In all three tests, Nestorone was the most potent progestin. The progestational activity of Nestorone was also compared after oral and s.c. administration in rabbits. The potency of Nestorone was over 100-fold higher upon s.c. administration than via the oral route. The androgenic activity of progestins, based on the stimulation of ventral prostate (androgenic target) and levator ani (anabolic target) growth in castrated immature rats, showed good correlation with their binding affinity to AR. Nestorone showed no androgenic or anabolic activity. Nestorone did not bind to sex hormone binding globulin (SHBG), whereas both levonorgestrel and 3-keto-desogestrel showed significant binding to SHBG. The estrogenic/antiestrogenic activity of Nestorone was investigated in immature ovariectomized rats. In contrast to estradiol and levonorgestrel, Nestorone showed no uterotropic activity in ovariectomized rats. Despite significant binding to glucocorticoid receptors (GR), Nestorone showed no glucocorticoid activity in vivo. It is concluded that a strong progestational activity, combined with lack of androgenic, estrogenic, and glucocorticoid-like activities, confer special advantages to Nestorone for use in contraception and hormone replacement therapy.
American Journal of Reproductive Immunology | 1990
Ladd A; Yun-Yen Tsong; Lok J; Rosemarie B. Thau
ABSTRACT: Active immunization against LHRH is a promising method of contraception for men. In order to be acceptable, sufficient amounts of anti‐LHRH antibodies must be induced rapidly after vaccination. In previously reported animal studies, we found that it took considerable time (up to 5 months) to obtain antibody titers (AT) that were sufficiently high for complete suppression of spermatogenesis. The possibility of accelerating the immune response to LHRH by increasing the dose of immunogen was investigated in the male rat. Six doses of LHRH conjugated to tetanus toxoid (TT) in the 10 position (LHRH10‐TT), ranging from 2.5 to 612 μg, and three doses of LHRH1‐TT (50 to 612 μg) were tested. The magnitude of the immune response did not depend on the dose of the antigen, provided a threshold dose had been surpassed. Antigenicity of LHRH conjugated to TT at either the 1‐, 6‐, or 10‐position was compared in rats and rabbits. In both species LHRH1‐TT induced sufficient antibody concentrations to suppress pituitary gonadotropins (LH and FSH) and, subsequently, serum testosterone (T) levels faster than either the 6‐ or 10‐conjugates. Only materials permitted for use in humans were utilized in these experiments. Conclusion: Active immunization against LHRH conjugated to TT at the 1‐position has potential as a fast, convenient method of male contraception.
Journal of Reproductive Immunology | 1989
Ladd A; Yun-Yen Tsong; G. Prabhu; Rosemarie B. Thau
The possibility of immunological suppression of spermatogenesis while normal libido is maintained by exogenous androgen supplementation was tested in male rats. Neither short- nor long-term treatment with androgen (testosterone-17-trans-4-N-butyl-cyclohexane carboxylate) alone influenced fertility. Active immunization against LHRH administered simultaneously with exogenous androgen supplement caused infertility in 100% of the tested animals, all of which displayed normal sexual behavior. The atrophy of the testes and accessory sex organs was reversible.
Contraception | 2010
Robert M. Brenner; Ov D. Slayden; Anita Nath; Yun-Yen Tsong; Regine Sitruk-Ware
BACKGROUND Ulipristal (UPA; CDB-2914) is a progesterone receptor modulator with contraceptive potential. To test its effects when delivered by an intrauterine system (IUS), we prepared control and UPA-filled IUS and evaluated their effects in rhesus macaques. STUDY DESIGN Short lengths of Silastic tubing either empty (n=3) or containing UPA (n=5) were inserted into the uteri of 8 ovariectomized macaques. Animals were cycled by sequential treatment with estradiol and progesterone. After 3.5 cycles, the uterus was removed. RESULTS During treatment, animals with an empty IUS menstruated for a mean total of 11.66+/-0.88 days, while UPA-IUS treated animals bled for only 1+/-0.45 days. Indices of endometrial proliferation were significantly reduced by UPA-IUS treatment. The UPA exposed endometria were atrophied with some glandular cysts while the blank controls displayed a proliferative morphology without cysts. Androgen receptors were more intensely stained in the glands of the UPA-IUS treated endometria than in the blank-IUS treated controls. CONCLUSIONS In rhesus macaques, a UPA-IUS induced endometrial atrophy and amenorrhea. The work provides proof of principle that an IUS can deliver effective intrauterine concentrations of Ulipristal.
Menopause | 2007
Charles E. Wood; Regine Sitruk-Ware; Yun-Yen Tsong; Thomas C. Register; Cynthia J. Lees; J. Mark Cline
Objective:To evaluate the effects of oral estradiol given with either oral or intravaginal micronized progesterone (P4) on risk biomarkers for breast cancer in a postmenopausal monkey model. Design:This experiment was a two-way crossover study in which 20 ovariectomized adult female cynomolgus macaques were treated (in equivalent doses for women) with oral estradiol (1 mg/d) + oral micronized P4 (200 mg/d) or intravaginal P4 delivered by Silastic rings (6- to 10-mg/d release rate). Hormone treatments lasted 2 months and were separated by a 1-month washout period. The primary outcome measure was breast epithelial proliferation. Results:Serum P4 concentrations were significantly greater in subjects receiving oral P4 (10.9 ng/mL) compared with intravaginal P4 (3.8 ng/mL) at 2 to 3 hours after oral dosing (P < 0.0001) but not at 24 to 28 hours after oral dosing (2.9 ng/mL for oral P4 vs 3.2 ng/mL for intravaginal P4 at 2 months, P = 0.19). Serum estradiol concentrations were significantly lower after oral P4 than after intravaginal P4 (P < 0.05 for all time points). Oral P4 resulted in significantly decreased body weight (−2.5%) compared with intravaginal P4 (+3.6%) (P = 0.0001). Markers of breast proliferation, sex steroid receptor expression, and endometrial area did not differ significantly between oral P4 and intravaginal P4 treatments (P > 0.1 for all). Conclusions:Despite different pharmacodynamic profiles, oral and intravaginal P4 had similar effects on biomarkers in the postmenopausal breast.
Psychoneuroendocrinology | 2007
Carol A. Shively; Charles E. Wood; Thomas C. Register; Stephanie L. Willard; Cynthia J. Lees; Haiying Chen; Regine Sitruk-Ware; Yun-Yen Tsong; J. Mark Cline
The purpose of the experiments reported here was to investigate central nervous system effects of commonly prescribed postmenopausal hormone therapies in a primate model, the cynomolgus monkey (Macaca fascicularis). The results of two experiments are reported. In the first, ovariectomized adult cynomolgus monkeys were treated for eight weeks each with oral micronized 17beta-estradiol (E2) (n=23), E2+medroxyprogesterone acetate (MPA) (n=23), E2+progesterone (P4) (n=23), and placebo (n=23) using a crossover design. In the second, ovariectomized adult cynomolgus monkeys were treated for eight weeks with oral micronized E2+oral micronized P4 (n=10), or E2+intravaginal micronized P4 delivered via a Silastic ring (n=8), or oral placebo and intravaginal placebo (n=5), using a parallel arm design. Behavior was recorded during weeks two through four. Cerebrospinal fluid (CSF) and blood were sampled, and 24h heart rate recorded by telemetry during weeks five through seven. Monoaminergic metabolites were assayed in CSF, and cortisol was assayed in serum. There were no significant effects of treatment on CSF monoaminergic metabolites or heart rate. E2+MPA increased cortisol concentrations. While there were some differences in effects between experiments, both progestogens and both routes of administration increased time spent resting, particularly resting in body contact, resulting in increased passive affiliative interaction. Thus, synthetic progestogens appear to be as sedating as progesterone, and the ring delivery system does not appear to protect the central nervous system from effects of progestogens. Further research is needed to explore social context as an important feature of behavioral response to steroid hormone regimens and to verify and extend knowledge of systemic effects of vaginal ring-delivered progestogens.
Journal of Reproductive Immunology | 1985
Harold A. Nash; C.C. Chang; Yun-Yen Tsong
Earlier tests of an antipregnancy vaccine consisting of the beta-subunit of human chorionic gonadotropin (beta-hCG) linked by reaction with a carbodiimide reagent to tetanus toxoid (TT) and adsorbed on Al(OH)3 resulted in antibody responses that were judged inadequate in some women. Experiments were therefore conducted to evaluate the effectiveness of additional adjuvants in increasing the antibody response. Muramyl dipeptide (MDP) and several of its analogs were formulated with the vaccine and tested in rabbits. Some of the analogs, and notably N-acetyl-normuramyl-L-alanyl-D-isoglutamine, elicited substantial increments in the ability of the antisera to bind [125I]hCG and in its ability to neutralize hCG in the rat uterine weight assay. The effectiveness of these peptides was greatest when formulated in a water-in-oil emulsion. Increments of 10 fold were attained using a vegetable oil as the oil component. The MDP analogs were much less effective as adjuvants when formulated in oil-in-water emulsions or in aqueous suspensions of the antigen. It is concluded that selected MDP analogs incorporated in a water-in-vegetable oil emulsion can markedly increase the circulating antibody response to the beta-hCG-TT vaccine.
Journal of Reproductive Immunology | 1985
Yun-Yen Tsong; C.C. Chang; Harold A. Nash
Abstract The antibody response obtained after vaccinating rabbits with the β-subunit of human chorionic gonadotropin (β-hCG) linked to several protein and polysaccharide carriers was measured. In all but one preparation, carbodiimide was used to couple the β-hCG to the carrier. Tetanus toxoid (TT) and cholera vaccine proved the most effective carriers among those examined. TT from different manufacturers proved to be greatly different in free amino group content and differed in ability to participate in the coupling reaction. Reasonably good replication of the coupling reaction was obtained with different production lots from the same manufacturer. Inferior antigenic response was obtained with the products of coupling β-hCG to H. pertussis , influenza vaccine, polylysine, pneumococcus polysaccharide, or E. coli polysaccharide. The findings indicate TT and cholera vaccine to be especially effective in enhancing the antigenicity of a weakly antigenic peptide but point to significant differences in the TT from different manufacturers.
Journal of Reproductive Immunology | 1986
C.C. Chang; Harold A. Nash; Yun-Yen Tsong
Abstract Experiments were conducted in rabbits to determine the effect of adjuvant use on the antibody response following booster injections. The antigen used was in all cases the β-subunit of human chorionic gonadotropin linked to tetanus toxoid (β-hCG-TT). Adjuvants used were Al(OH) 3 , MDP analogs, and a streptococcus preparation, OK432. Primary vaccinations included Al(OH) 3 adjuvant with or without supplementary adjuvants. In general, the greater the antibody response following primary vaccination, the greater the response following booster vaccination whether or not adjuvant was used in the booster. No increment in antibody titers was found by reason of including MDP analogs in booster vaccinations. OK432, in contrast, gave increased responses in booster injections which were in several cases statistically significant. The value of including Al(OH) 3 in booster injections is not clear from the experimental data. In no case was the increment due to its inclusion large.
Journal of Reproductive Immunology | 1985
C.C. Chang; Yun-Yen Tsong; Harold A. Nash
Abstract Rabbits were used to test the efficacy of several materials as supplementary adjuvants when administered as part of a vaccine formulation consisting of the β-subunit of human chorionic gonadotropin linked to tetanus toxoid (β-hCG-TT) and adsorbed on Al(OH) 3 . In the amounts used, Corynebacterium parvum , levamisole, thymic factor, and N , N -dioctadecyl- N ′- N ′-bis(2-hydroxyethyl)propanediamine exhibited little adjuvant activity although the latter material elicited marginal increments when incorporated in liposomes. A Salmonella lipopolysaccharide preparation (SPLPS) and a streptococcal preparation (OK-432) each gave approximately 7-fold increments in titer. The SPLPS preparation was pyrogenic at the doses used. OK-432 was nonpyrogenic and did not cause other evident undesirable effects. It may therefore prove to be a useful adjuvant. It gave a nearly flat dose response curve over the range of 0.5 to 4.0 mg per rabbit. Incorporation of β-hCG-TT on Al(OH) 3 in a water-in-oil emulsion caused a moderate increase in titers. Incorporation into liposomes or an oil-in-water emulsion was not effective.