Molecular genetics and genomics : MGG, Jan 7, 2017
The genetic risk of developing type 2 diabetes (T2D) increases in parallel with the proportion of... more The genetic risk of developing type 2 diabetes (T2D) increases in parallel with the proportion of Native American ancestry. Mestizo Mexicans have a 70% Native Amerindian genetic background. The T130I polymorphism in the HNF4A gene has been associated with early-onset T2D in mestizo Mexicans. Thus, the aim of the present study was to evaluate the frequency and relationship of the T130I variant in the HNF4A gene with risk factors for developing T2D in eleven indigenous groups from Mexico. In two groups, all exons of the HNF4A gene were directly sequenced; in the remaining the T130I polymorphism was analyzed by restriction fragment length polymorphism. Ancestry informative markers were assessed to confirm the Amerindian component. An additional analysis of EHH was carried out. Interestingly, HNF4A gene screening revealed only the presence of the T130I polymorphism. The range frequency of the risk allele (T) in the indigenous groups was from 2.7 to 16%. Genotypic frequencies (T130I/I130...
Association of type 2 diabetes (T2D) with common variants in HHEX, HNF4α, KCNJ11, PPARγ, CDKN2A/2... more Association of type 2 diabetes (T2D) with common variants in HHEX, HNF4α, KCNJ11, PPARγ, CDKN2A/2B, SLC30A8, CDC123/CAMK1D, TCF7L2, ABCA1 and SLC16A11 genes have been reported, mainly in populations of European and Asian ancestry and to a lesser extent in Latin Americans. Thus, we aimed to investigate the contribution of rs1111875 (HHEX), rs1800961 (HNF4α), rs5219 (KCNJ11), rs1801282 (PPARγ), rs10811661 (CDKN2A/2B), rs13266634 (SLC30A8), rs12779790 (CDC123/CAMK1D), rs7903146 (TCF7L2), rs9282541 (ABCA1) and rs13342692 (SLC16A11) polymorphisms in the genetic background of Maya population to associate their susceptibility to develop T2D. This is one of the first studies designed specifically to investigate the inherited component of T2D in indigenous population of Mexico. SNPs were genotyped by allelic discrimination method in 575 unrelated Maya individuals. Two SNPs rs10811661 and rs928254 were significantly associated with T2D after adjusting for BMI; rs10811661 in a recessive and rs...
We describe a time-resolved immunofluorometric assay (TR-IFMA) for human 17 beta-hydroxysteroid d... more We describe a time-resolved immunofluorometric assay (TR-IFMA) for human 17 beta-hydroxysteroid dehydrogenase (17HSD) in which antibody-coated microtiter strip wells and europium chelate-labeled polyclonal antibodies are used. In preparing the label, a polyclonal antibody is affinity-purified and derivatized with diethylenetriamine-pentaacetic acid. With this derivative, five to eight europium ions can be combined with one antibody molecule without decreasing the antibody's immunoreactivity. The minimum detectable concentration of 17HSD is 0.13 microgram/L; the intra- and interassay CVs are less than 8% and less than 15%, respectively, for concentrations between 0.3 and 100 micrograms/L. There is no difference between the concentrations of 17HSD in plasma specimens taken during the proliferative and luteal phases of the menstrual cycle, the measured mean concentration being 0.22 microgram/L. We found no correlation between plasma 17HSD and progesterone concentrations. The plasma...
Estradiol esters at C-17 and C-3 with palmitic, stearic and oleic acids were chemically synthesiz... more Estradiol esters at C-17 and C-3 with palmitic, stearic and oleic acids were chemically synthesized and then evaluated for their long-acting estrogenic responses in ovariectomized rats. The duration of the biological effects was measured after a single subcutaneous dose of 0.1 mumol of each ester and compared with those observed with 17 beta-estradiol, estradiol 3-benzoate and estradiol 17-enanthate. Vaginal citology, uterophyc action, serum gonadotropins inhibition and 17 beta-estradiol levels were measured 0, 5, 10, 20, 30 and 60 days after injection. The results disclosed that most of the estradiol derivatives evaluated exhibited a long-acting estrogenic action. However, the monoesters at C-17 showed longer effects that monoesters at C-3, while the estradiol diesters exhibited the shortest effects. In addition as shown by its low serum levels, all estradiol esters with unsaturated fatty acids show a decreased E2 absorption. The overall results indicated that esterification of E2 with long chain fatty acids provided long-acting properties to it, being higher with C-17 esters. Whether some of these compounds could be employed in substitutive endocrine therapy remains to be established.
The Journal of Steroid Biochemistry and Molecular Biology, 1993
The short term effects of norethisterone (NET), progesterone (P), estradiol (E2) and dihydrotesto... more The short term effects of norethisterone (NET), progesterone (P), estradiol (E2) and dihydrotestosterone (DHT) on the gonadotropin secretion of pituitary cells, from both male and female rats, in primary culture primed with E2 were studied. In female cells, NET only increased the GnRH-induced secretion of LH, while P increased both LH and FSH. Male pituitary cells showed an increased response to GnRH after P pretreatment only if the E2 concentration was augmented. However with the same E2 conditions pretreatment with NET decreased the stimulated LH, but not FSH secretion. Pretreatment with E2 inhibited LH stimulated secretion from pituitary cells of male but not female rats. Furthermore DHT treatment diminished the GnRH response for both LH and FSH in pituitary cells from both sexes. Androgen pretreatment increased basal gonadotropin secretion in male but not in female cells. Basal FSH secretion was increased by NET pretreatment in male cells. This suggests that NET is metabolized by cultured pituitary cells to A-ring reduced compounds during the 4 h incubation period. The formation of NET metabolites, particularly the 3 beta, 5 alpha and 5 alpha-NET might be responsible for the estrogenic and androgenic effects observed when NET was administered to the cultured pituitary cells.
In this study, we investigated the effects of pentolame, a 17 beta-aminoestrogen derivative, upon... more In this study, we investigated the effects of pentolame, a 17 beta-aminoestrogen derivative, upon coagulation, serum LH, pituitary progestin receptors, uterine weight, and endometrium morphological changes in the castrated female rat. Groups of animals were subcutaneously (s.c.) injected with either estradiol (E2) (0.1 up to 1000 micrograms/animal), pentolame (1 up to 1000 micrograms/animal), or the vehicle alone daily for 5 consecutive days starting 2 weeks following ovariectomy. Administration of pentolame (10 to 1000 micrograms/animal) increased significantly (p < 0.05) the blood clotting time when compared with that obtained in the group of control animals (EC50 582 micrograms). Pentolame (500 and 1000 micrograms/rat for 5 days) caused a significant inhibition (p < 0.01) of serum LH levels (IC50 860 micrograms), which remained suppressed until Day 5 post last injection. In addition, treatment with pentolame was able to restore in the castrated female rat the presence of specific estrogen-dependent progestin binding sites at the anterior pituitary level. The affinity constants and the number of binding sites of pentolame-induced progestin receptors were similar to those obtained with estradiol at equipotent doses (860 micrograms vs. 1 microgram/animal, respectively). Administration of the 17 beta-aminoestrogen derivative resulted in a significant increase in uterine weight (EC50 420 micrograms) and endometrial characteristics were indistinguishable from those observed in the group of rats treated with E2.
Previous studies have sought to associate the Pro12Ala variant of the peroxisome proliferator-act... more Previous studies have sought to associate the Pro12Ala variant of the peroxisome proliferator-activated receptor gamma2 (PPARG2) gene with type 2 diabetes, insulin resistance, and obesity, with controversial results. We have determined the Pro12Ala variant frequency in 370 nondiabetic Mexican Mestizo subjects and in five Mexican Amerindian groups and have investigated its possible association with lipid metabolism, insulin serum levels, and obesity in three of these populations. Two independent case-control studies were conducted in 239 nondiabetic individuals: 135 case subjects (BMI > or = 25 kg/m2) and 104 control subjects (BMI < 25 kg/m2). The PPARG2 Ala12 allele frequency was higher in most Amerindian populations (0.17 in Yaquis, 0.16 in Mazahuas, 0.16 in Mayans, and 0.20 in Triquis) than in Asians, African Americans, and Caucasians. The Pro12Ala and Ala12Ala (X12Ala) genotypes were significantly associated with greater BMI in Mexican Mestizos and in two Amerindian groups. X12Ala individuals had a higher risk of overweight or obesity than noncarriers in Mestizos (OR = 3.67; 95% CI, 1.42-9.48; p = 0.007) and in Yaquis plus Mazahuas (OR = 3.21; 95% CI, 1.27-8.11; p = 0.013). Our results provide further support of the association between the PPARG2 Ala12 allele and risk of overweight or obesity in Mestizos and two Amerindian populations from Mexico.
To determine the effects of immunization with an anti-LH-releasing hormone (LH-RH) vaccine in pos... more To determine the effects of immunization with an anti-LH-releasing hormone (LH-RH) vaccine in postmenopausal women. Pilot clinical study. Normal human volunteers in a medical research-training environment. Three postmenopausal women with a mean age of 60 years, 5 years of amenorrhea, and severe hypoestrogenism with elevated serum LH and FSH. Intramuscular immunization with 300 micrograms LH-RH equivalent of the vaccine in two occasions 1 month apart. Patients were followed for clinical assessment and serum LH, FSH, and anti-LH-RH titers at regular monthly intervals for 7 months. The injection of the anti-LH-RH vaccine followed by a booster injection 1 month later resulted in a sharp decrease, 60 days after the first injection, of both serum gonadotropins, accompanied by an increase in anti-LH-RH antibody titers, which were reversible after 180 days in the absence of further booster immunization. Active immunization offer a safe option to induce antibody response, which in the present regime employed was of about 6-months duration. This procedure opens new possibilities for its use as an affordable therapeutic agent in some hormone-dependent clinical conditions.
. To assess whether structural modifications on the A-ring of norethisterone (NET) could modify i... more . To assess whether structural modifications on the A-ring of norethisterone (NET) could modify its antigonadotropic potency, comparative studies using NET, 5α-dihydro NET (5α-NET) and its 3β,5α and 3α,5α tetrahydro derivatives in castrated adult rats were undertaken. The antigonadotropic effect of these compounds was evaluated by measuring the serum and pituitary immunoreactive concentrations of LH and FSH following their chronic sc administration to animals depleted of progesterone receptors. The results demonstrated that 3β,5α-NET and 5α-dihydro-NET exhibited a significantly greater gonadotropic inhibiting activity as compared with that of their parent compound. The simultaneous administration of tamoxifen with 3β,5α-NET resulted in a significant diminution of its antigonadotropic potency, particularly for LH. These data indicate that the potent antigonadotropic effect of 3β,5α-NET metabolite was mediated via oestrogen receptors. The LH inhibitory activity of 5α-dihydro-NET was not suppressed by the non-steroidal antioestrogen administration, thus suggesting that 5α-NET might exert its effect via androgen receptors. The overall data were interpreted as demonstrating that metabolic conversion products of NET exhibit potent antigonadotropic effect. The data are consistent with an A-ring enhancement of the antigonadotropic potency of this synthetic progestin and open an alternate approach to the development of fertility regulating agents.
Menjívar M, Vilchis F, Cárdenas M, Cruz C, Merchant H, Pérez-Palacios G, Pedraza-Chaverri J. Pitu... more Menjívar M, Vilchis F, Cárdenas M, Cruz C, Merchant H, Pérez-Palacios G, Pedraza-Chaverri J. Pituitary–ovarian dysfunction in rats with induced nephrotic syndrome. Eur J Endocrinol 1995; 132:502–6. ISSN 0804–4643 The reproductive hormonal profile was evaluated in female rats with experimental nephrotic syndrome induced with a single subcutaneous dose of puromycin aminonucleoside (PAN). Serum concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH), progesterone (P4), testosterone and 17β-estradiol (E2) were determined sequentially in control and experimental groups on days 1,3,7 and 10 after PAN administration. Prolactin levels were also assessed on day 10. In both groups, vaginal smears were taken daily throughout the study to evaluate cyclic histological changes. At the end of the experiment the histological appearance of the ovaries was evaluated by light microscopy. Nephrotic rats had a rapid loss of the estrous cycle starting on day 4, which set them at di...
... Nacional Autónoma de México, Mexico City, Mexico: Salvador Ramírez-Jimenez, Leonor Jacobo, Ma... more ... Nacional Autónoma de México, Mexico City, Mexico: Salvador Ramírez-Jimenez, Leonor Jacobo, Margarita ... Mexico City, Mexico: Ivette Cruz-Bautista, Daniela Riaño, Cristina García-Ulloa, Lorena ... Juárez de México, Mexico City, Mexico: Guadalupe Ortíz-López, María de los ...
A pilot study to assess the use of natural hormones in macrocrystalline sustained release system ... more A pilot study to assess the use of natural hormones in macrocrystalline sustained release system was undertaken in normal menstruating women. Progesterone at a dose of 100 mg in combination with 5 mg estradiol-17 beta aqueous macrocrystalline suspension (3ml) of defined particle size range (100-250 microns) were administered to five female volunteers of reproductive age, on day 5 of their normal menstrual cycles and then every 28 days consecutively for the next two months. Peripheral venous blood samples were obtained from the women three times a week for 60 days after the third injection for the measurement of serum progesterone, estradiol-17 beta, LH and FSH. The menstrual bleeding patterns were closely monitored during the study period. The results obtained indicate that the exogenous hormone administration produces blood levels similar to those observed during the luteal phase of the menstrual cycle. Follicular maturation as assessed by endogenous estradiol rise, above 150 pg/ml, occurred 29.7 days s.d. 6.4 after the injection. Ovulation as measured by progesterone levels above 5 ng/ml was documented 34.4 days s.d. 4.3 after the third injection. The bleeding patterns were regular though initially shorter but these increased progressively towards normal pattern during course of the study. The data suggest that progesterone/estradiol-17 beta combination administered as an aqueous macrocrystalline suspension is capable of producing sustained ovulation inhibition and could be applied in the design of new once-a-month injectable contraceptives.
Molecular genetics and genomics : MGG, Jan 7, 2017
The genetic risk of developing type 2 diabetes (T2D) increases in parallel with the proportion of... more The genetic risk of developing type 2 diabetes (T2D) increases in parallel with the proportion of Native American ancestry. Mestizo Mexicans have a 70% Native Amerindian genetic background. The T130I polymorphism in the HNF4A gene has been associated with early-onset T2D in mestizo Mexicans. Thus, the aim of the present study was to evaluate the frequency and relationship of the T130I variant in the HNF4A gene with risk factors for developing T2D in eleven indigenous groups from Mexico. In two groups, all exons of the HNF4A gene were directly sequenced; in the remaining the T130I polymorphism was analyzed by restriction fragment length polymorphism. Ancestry informative markers were assessed to confirm the Amerindian component. An additional analysis of EHH was carried out. Interestingly, HNF4A gene screening revealed only the presence of the T130I polymorphism. The range frequency of the risk allele (T) in the indigenous groups was from 2.7 to 16%. Genotypic frequencies (T130I/I130...
Association of type 2 diabetes (T2D) with common variants in HHEX, HNF4α, KCNJ11, PPARγ, CDKN2A/2... more Association of type 2 diabetes (T2D) with common variants in HHEX, HNF4α, KCNJ11, PPARγ, CDKN2A/2B, SLC30A8, CDC123/CAMK1D, TCF7L2, ABCA1 and SLC16A11 genes have been reported, mainly in populations of European and Asian ancestry and to a lesser extent in Latin Americans. Thus, we aimed to investigate the contribution of rs1111875 (HHEX), rs1800961 (HNF4α), rs5219 (KCNJ11), rs1801282 (PPARγ), rs10811661 (CDKN2A/2B), rs13266634 (SLC30A8), rs12779790 (CDC123/CAMK1D), rs7903146 (TCF7L2), rs9282541 (ABCA1) and rs13342692 (SLC16A11) polymorphisms in the genetic background of Maya population to associate their susceptibility to develop T2D. This is one of the first studies designed specifically to investigate the inherited component of T2D in indigenous population of Mexico. SNPs were genotyped by allelic discrimination method in 575 unrelated Maya individuals. Two SNPs rs10811661 and rs928254 were significantly associated with T2D after adjusting for BMI; rs10811661 in a recessive and rs...
We describe a time-resolved immunofluorometric assay (TR-IFMA) for human 17 beta-hydroxysteroid d... more We describe a time-resolved immunofluorometric assay (TR-IFMA) for human 17 beta-hydroxysteroid dehydrogenase (17HSD) in which antibody-coated microtiter strip wells and europium chelate-labeled polyclonal antibodies are used. In preparing the label, a polyclonal antibody is affinity-purified and derivatized with diethylenetriamine-pentaacetic acid. With this derivative, five to eight europium ions can be combined with one antibody molecule without decreasing the antibody's immunoreactivity. The minimum detectable concentration of 17HSD is 0.13 microgram/L; the intra- and interassay CVs are less than 8% and less than 15%, respectively, for concentrations between 0.3 and 100 micrograms/L. There is no difference between the concentrations of 17HSD in plasma specimens taken during the proliferative and luteal phases of the menstrual cycle, the measured mean concentration being 0.22 microgram/L. We found no correlation between plasma 17HSD and progesterone concentrations. The plasma...
Estradiol esters at C-17 and C-3 with palmitic, stearic and oleic acids were chemically synthesiz... more Estradiol esters at C-17 and C-3 with palmitic, stearic and oleic acids were chemically synthesized and then evaluated for their long-acting estrogenic responses in ovariectomized rats. The duration of the biological effects was measured after a single subcutaneous dose of 0.1 mumol of each ester and compared with those observed with 17 beta-estradiol, estradiol 3-benzoate and estradiol 17-enanthate. Vaginal citology, uterophyc action, serum gonadotropins inhibition and 17 beta-estradiol levels were measured 0, 5, 10, 20, 30 and 60 days after injection. The results disclosed that most of the estradiol derivatives evaluated exhibited a long-acting estrogenic action. However, the monoesters at C-17 showed longer effects that monoesters at C-3, while the estradiol diesters exhibited the shortest effects. In addition as shown by its low serum levels, all estradiol esters with unsaturated fatty acids show a decreased E2 absorption. The overall results indicated that esterification of E2 with long chain fatty acids provided long-acting properties to it, being higher with C-17 esters. Whether some of these compounds could be employed in substitutive endocrine therapy remains to be established.
The Journal of Steroid Biochemistry and Molecular Biology, 1993
The short term effects of norethisterone (NET), progesterone (P), estradiol (E2) and dihydrotesto... more The short term effects of norethisterone (NET), progesterone (P), estradiol (E2) and dihydrotestosterone (DHT) on the gonadotropin secretion of pituitary cells, from both male and female rats, in primary culture primed with E2 were studied. In female cells, NET only increased the GnRH-induced secretion of LH, while P increased both LH and FSH. Male pituitary cells showed an increased response to GnRH after P pretreatment only if the E2 concentration was augmented. However with the same E2 conditions pretreatment with NET decreased the stimulated LH, but not FSH secretion. Pretreatment with E2 inhibited LH stimulated secretion from pituitary cells of male but not female rats. Furthermore DHT treatment diminished the GnRH response for both LH and FSH in pituitary cells from both sexes. Androgen pretreatment increased basal gonadotropin secretion in male but not in female cells. Basal FSH secretion was increased by NET pretreatment in male cells. This suggests that NET is metabolized by cultured pituitary cells to A-ring reduced compounds during the 4 h incubation period. The formation of NET metabolites, particularly the 3 beta, 5 alpha and 5 alpha-NET might be responsible for the estrogenic and androgenic effects observed when NET was administered to the cultured pituitary cells.
In this study, we investigated the effects of pentolame, a 17 beta-aminoestrogen derivative, upon... more In this study, we investigated the effects of pentolame, a 17 beta-aminoestrogen derivative, upon coagulation, serum LH, pituitary progestin receptors, uterine weight, and endometrium morphological changes in the castrated female rat. Groups of animals were subcutaneously (s.c.) injected with either estradiol (E2) (0.1 up to 1000 micrograms/animal), pentolame (1 up to 1000 micrograms/animal), or the vehicle alone daily for 5 consecutive days starting 2 weeks following ovariectomy. Administration of pentolame (10 to 1000 micrograms/animal) increased significantly (p < 0.05) the blood clotting time when compared with that obtained in the group of control animals (EC50 582 micrograms). Pentolame (500 and 1000 micrograms/rat for 5 days) caused a significant inhibition (p < 0.01) of serum LH levels (IC50 860 micrograms), which remained suppressed until Day 5 post last injection. In addition, treatment with pentolame was able to restore in the castrated female rat the presence of specific estrogen-dependent progestin binding sites at the anterior pituitary level. The affinity constants and the number of binding sites of pentolame-induced progestin receptors were similar to those obtained with estradiol at equipotent doses (860 micrograms vs. 1 microgram/animal, respectively). Administration of the 17 beta-aminoestrogen derivative resulted in a significant increase in uterine weight (EC50 420 micrograms) and endometrial characteristics were indistinguishable from those observed in the group of rats treated with E2.
Previous studies have sought to associate the Pro12Ala variant of the peroxisome proliferator-act... more Previous studies have sought to associate the Pro12Ala variant of the peroxisome proliferator-activated receptor gamma2 (PPARG2) gene with type 2 diabetes, insulin resistance, and obesity, with controversial results. We have determined the Pro12Ala variant frequency in 370 nondiabetic Mexican Mestizo subjects and in five Mexican Amerindian groups and have investigated its possible association with lipid metabolism, insulin serum levels, and obesity in three of these populations. Two independent case-control studies were conducted in 239 nondiabetic individuals: 135 case subjects (BMI > or = 25 kg/m2) and 104 control subjects (BMI < 25 kg/m2). The PPARG2 Ala12 allele frequency was higher in most Amerindian populations (0.17 in Yaquis, 0.16 in Mazahuas, 0.16 in Mayans, and 0.20 in Triquis) than in Asians, African Americans, and Caucasians. The Pro12Ala and Ala12Ala (X12Ala) genotypes were significantly associated with greater BMI in Mexican Mestizos and in two Amerindian groups. X12Ala individuals had a higher risk of overweight or obesity than noncarriers in Mestizos (OR = 3.67; 95% CI, 1.42-9.48; p = 0.007) and in Yaquis plus Mazahuas (OR = 3.21; 95% CI, 1.27-8.11; p = 0.013). Our results provide further support of the association between the PPARG2 Ala12 allele and risk of overweight or obesity in Mestizos and two Amerindian populations from Mexico.
To determine the effects of immunization with an anti-LH-releasing hormone (LH-RH) vaccine in pos... more To determine the effects of immunization with an anti-LH-releasing hormone (LH-RH) vaccine in postmenopausal women. Pilot clinical study. Normal human volunteers in a medical research-training environment. Three postmenopausal women with a mean age of 60 years, 5 years of amenorrhea, and severe hypoestrogenism with elevated serum LH and FSH. Intramuscular immunization with 300 micrograms LH-RH equivalent of the vaccine in two occasions 1 month apart. Patients were followed for clinical assessment and serum LH, FSH, and anti-LH-RH titers at regular monthly intervals for 7 months. The injection of the anti-LH-RH vaccine followed by a booster injection 1 month later resulted in a sharp decrease, 60 days after the first injection, of both serum gonadotropins, accompanied by an increase in anti-LH-RH antibody titers, which were reversible after 180 days in the absence of further booster immunization. Active immunization offer a safe option to induce antibody response, which in the present regime employed was of about 6-months duration. This procedure opens new possibilities for its use as an affordable therapeutic agent in some hormone-dependent clinical conditions.
. To assess whether structural modifications on the A-ring of norethisterone (NET) could modify i... more . To assess whether structural modifications on the A-ring of norethisterone (NET) could modify its antigonadotropic potency, comparative studies using NET, 5α-dihydro NET (5α-NET) and its 3β,5α and 3α,5α tetrahydro derivatives in castrated adult rats were undertaken. The antigonadotropic effect of these compounds was evaluated by measuring the serum and pituitary immunoreactive concentrations of LH and FSH following their chronic sc administration to animals depleted of progesterone receptors. The results demonstrated that 3β,5α-NET and 5α-dihydro-NET exhibited a significantly greater gonadotropic inhibiting activity as compared with that of their parent compound. The simultaneous administration of tamoxifen with 3β,5α-NET resulted in a significant diminution of its antigonadotropic potency, particularly for LH. These data indicate that the potent antigonadotropic effect of 3β,5α-NET metabolite was mediated via oestrogen receptors. The LH inhibitory activity of 5α-dihydro-NET was not suppressed by the non-steroidal antioestrogen administration, thus suggesting that 5α-NET might exert its effect via androgen receptors. The overall data were interpreted as demonstrating that metabolic conversion products of NET exhibit potent antigonadotropic effect. The data are consistent with an A-ring enhancement of the antigonadotropic potency of this synthetic progestin and open an alternate approach to the development of fertility regulating agents.
Menjívar M, Vilchis F, Cárdenas M, Cruz C, Merchant H, Pérez-Palacios G, Pedraza-Chaverri J. Pitu... more Menjívar M, Vilchis F, Cárdenas M, Cruz C, Merchant H, Pérez-Palacios G, Pedraza-Chaverri J. Pituitary–ovarian dysfunction in rats with induced nephrotic syndrome. Eur J Endocrinol 1995; 132:502–6. ISSN 0804–4643 The reproductive hormonal profile was evaluated in female rats with experimental nephrotic syndrome induced with a single subcutaneous dose of puromycin aminonucleoside (PAN). Serum concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH), progesterone (P4), testosterone and 17β-estradiol (E2) were determined sequentially in control and experimental groups on days 1,3,7 and 10 after PAN administration. Prolactin levels were also assessed on day 10. In both groups, vaginal smears were taken daily throughout the study to evaluate cyclic histological changes. At the end of the experiment the histological appearance of the ovaries was evaluated by light microscopy. Nephrotic rats had a rapid loss of the estrous cycle starting on day 4, which set them at di...
... Nacional Autónoma de México, Mexico City, Mexico: Salvador Ramírez-Jimenez, Leonor Jacobo, Ma... more ... Nacional Autónoma de México, Mexico City, Mexico: Salvador Ramírez-Jimenez, Leonor Jacobo, Margarita ... Mexico City, Mexico: Ivette Cruz-Bautista, Daniela Riaño, Cristina García-Ulloa, Lorena ... Juárez de México, Mexico City, Mexico: Guadalupe Ortíz-López, María de los ...
A pilot study to assess the use of natural hormones in macrocrystalline sustained release system ... more A pilot study to assess the use of natural hormones in macrocrystalline sustained release system was undertaken in normal menstruating women. Progesterone at a dose of 100 mg in combination with 5 mg estradiol-17 beta aqueous macrocrystalline suspension (3ml) of defined particle size range (100-250 microns) were administered to five female volunteers of reproductive age, on day 5 of their normal menstrual cycles and then every 28 days consecutively for the next two months. Peripheral venous blood samples were obtained from the women three times a week for 60 days after the third injection for the measurement of serum progesterone, estradiol-17 beta, LH and FSH. The menstrual bleeding patterns were closely monitored during the study period. The results obtained indicate that the exogenous hormone administration produces blood levels similar to those observed during the luteal phase of the menstrual cycle. Follicular maturation as assessed by endogenous estradiol rise, above 150 pg/ml, occurred 29.7 days s.d. 6.4 after the injection. Ovulation as measured by progesterone levels above 5 ng/ml was documented 34.4 days s.d. 4.3 after the third injection. The bleeding patterns were regular though initially shorter but these increased progressively towards normal pattern during course of the study. The data suggest that progesterone/estradiol-17 beta combination administered as an aqueous macrocrystalline suspension is capable of producing sustained ovulation inhibition and could be applied in the design of new once-a-month injectable contraceptives.
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