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Biomedical subjects

H H Goh

Publications and source records attributed to H H Goh.

At least 19 recordsLinked to original sources
PubMed2002

Functional characterization of a natural variant of luteinizing hormone.

Luteinizing hormone (LH) plays an important role in the gametogenesis in both sexes by promoting the production of sex steroid hormones in the testes and ovaries. We previously described a genetic variant (V) of LH resulted from a mutation (G1502A) in the LH beta-subunit gene, causing the glycine102serine change in the protein hormone. This variant was subsequently found to be associated with both male and female infertility. In this study, we determined the functional aspect of this LH variant in vitro. Site-directed mutagenesis was employed to construct the V-LH beta-subunit gene. Bioactivities of V-LH expressed in Chinese hamster ovary (CHO) cells cotransfected with the V-beta-subunit and native alpha-subunit genes were compared to those of wild-type (WT) LH. The amino acid replacement did not result in the change of efficacy of alpha- and beta-subunit dimerization of the hormone. However, V-LH had significantly lower receptor-binding activity (P<0.001) and lower biopotency for progesterone production (P<0.001) than WT-LH at the higher concentrations of LH. Considering the latter and its known association with both male and female infertility, it is suggested that the V-LH may be a contributing factor to the pathogenesis of infertility in the carriers of this variant.

Animals↗
PubMed2001

Dose-response effects of equine chorionic gonadotrophin (eCG) and human chorionic gonadotrophin (hCG) on early embryonic development and viable pregnancy rate in rats.

The present study examined the dose-response effects of eCG treatment alone and in combination with various doses of hCG on early embryonic development in vivo and viable pregnancy rate in rats. Mated female Wistar rats were treated with eCG alone (0, 10, 20 or 40 iu), or with 20 iu eCG in combination with various doses of hCG (10, 20, 40 or 80 iu) administered 48 h later. The animals were killed on days 2, 3, 4, 5 or 14 of pregnancy and the numbers of embryos and fetuses recovered were scored. All rats treated with 0 or 10 iu eCG were pregnant. The pregnancy rate was reduced from 62.5% on day 2 to 25% on day 14 and from 31% on day 2 to 10% on day 14 in the groups treated with 20 and 40 iu eCG, respectively. The reduction in pregnancy rate induced by 20 iu eCG was negated by the increasing doses of hCG used. A 100% pregnancy rate was noted on days 2 and 3 in the groups treated with doses of hCG between 10 and 80 iu and from day 2 to day 4 in the groups treated with doses of hCG between 20 and 80 iu. However, a higher viable pregnancy rate was observed only in the group treated with 10 iu hCG compared with the group treated with 20 iu eCG and 0 iu hCG. These results imply that hyperstimulation of rats with high doses of eCG compromises pregnancy rate and markedly reduces litter size and that the addition of hCG is required for complete ovulation, which results in higher embryo yield and a delay in early embryo demise.

Animals↗
PubMed1999

Association of molecular variants of luteinizing hormone with menstrual disorders.

OBJECTIVE: Luteinizing hormone (LH) promotes ovulation and luteinization of the ovarian follicle, and stimulates steroidogenesis in the ovaries. It is known to be present in different molecular forms, and secretion of abnormal LH has been implicated in menstrual disorders and infertility. The purpose of this study was to determine any association of two recently described LH variants with menstrual disorders in Singapore Chinese women. One of these variants had Trp8 to Arg8 and Ile15 to Thr15 replacements in the LH beta-subunit, while the second variant possessed Ser102 substitution for Gly102. PATIENTS: One hundred and seventy six patients with menstrual disorders and two hundred normal ovulatory women were recruited and screened for the presence of these two LH variants. METHODS: The polymerase chain reaction (PCR) products of patients were analysed by restriction fragment length polymorphism (RFLP) and the results were compared with those of normal ovulatory women and confirmed by DNA sequencing. RESULTS: Twenty one (11.9%) patients with menstrual disorders and twenty (10%) normal ovulatory women were found to carry the first variant, but its occurrence did not show any significant statistical difference between the patient and control groups (P = 0.679). However, the second variant was only detected in seven (4%) patients with menstrual disorders, and none of the normal ovulatory subjects (P = 0.005). CONCLUSIONS: the study showed that the first variant was not associated with menstrual disorders, whereas the second variant might be implicated in menstrual disorders in some Singapore Chinese women.

Adenoma↗
PubMed1997

Effects of hormone deficiency, androgen therapy and calcium supplementation on bone mineral density in female transsexuals.

A total of 79 healthy female transsexuals, divided into four groups, were involved in this study. Group 1 comprised 15 pre-operated normal cycling females; Group 2, five pre-operated females who were on regular androgen therapy for 1-3 years; Group 3, 27 post-operated females who were on regular androgen therapy for 2-12 years; and Group 4, 32 post-operated females who either had stopped or were on irregular androgen therapy. A bone scan of the lumber spine, at positions L2-L4, was carried out for each subject. A blood sample was taken for measurement of plasma testosterone concentrations. Ten subjects from Group 3 had a repeat bone scan following 10-39 months of calcium supplement (625 mg daily as calcium carbonate); another 10 post-operated females of Group 3 had a repeat bone scan 6-59 months later; and five subjects from Group 4 had a repeat scan following resumption of regular androgen therapy for 17-27 months. The mean +/- SE concentrations of testosterone of Groups 1-4 were, respectively, 0.58 +/- 0.05, 10.1 +/- 2.48, 7.7 +/- 0.98 and 0.99 +/- 0.14 ng/ml. Pre-operated females (Group 2) following 1-3 years of regular androgen therapy had significantly higher BMD and age-matched BMD than corresponding levels in pre-operated normal cycling females in Group 1. While the age-matched BMDs of post-operated females, who were on regular androgen therapy, were not significantly different, the mean BMD was significantly lower than corresponding values in the controls of Group 1. Post-operated females in Group 4 had significantly lower BMDs and age-matched BMDs as compared to corresponding values in controls of Group 1. The BMDs and age-matched BMDs of post-operated females, who were on regular androgen therapy, were significantly raised following daily calcium supplementation for durations ranging from 10-39 months. A repeat bone scan carried out following a lapse of 6-59 months did not reveal any significant change in the BMDs and age-matched BMDs of 10 post-operated females on regular androgen therapy. On the other hand, the BMDs and age-matched BMDs of post-operated females in Group 4 were significantly raised following the resumption of regular androgen therapy for 17-27 months. Results of the present study showed that ovariectomy and remaining in the hormone-deficient state for a sufficiently long duration was associated with a definite loss of bone mass. However, it was shown in this study that the resumption of regular androgen therapy for a sufficient duration could arrest this loss and, additionally, substantially increase the bone mass. Androgen appears to have a potentially greater impact on bone mass than oestrogen. Furthermore, calcium supplementation in a Singaporean population, which is accustomed to a low dietary calcium intake, can assist in the accretion of a higher bone mass in an adult population.

Adult↗
PubMed1995

Endocrine effects in Asian postmenopausal women, treated with SH D 461 M and Prempak-C.

We reported the results of a randomized cross-over study comparing SH D 461 M (Climen) and Prempak-C in 38 postmenopausal women who were established users of hormone replacement therapy (HRT). Climen contains 11 tablets of 2 mg estradiol valerate (EV), and 10 tablets with 2 mg EV plus 1 mg of cyproterone acetate. Prempak-C, on the other hand, is a regimen consisting of 28 tablets of 0.625 mg conjugated equine estrogens (CEE); the last 12 tablets are taken together with 0.15 mg of norgestrel (NG) tablets. Patients in Sequence I started with Climen for 6 months and then crossed-over to Prempak-C, for the next 6 months. Patients in Sequence II followed the reverse order. Following Climen treatment, significantly higher levels (P < 0.05, t-test) of sex hormone binding globulin (SHBG) and estradiol, when compared to Prempak-C treated subjects, were noted. No significant differences in follicle stimulating hormone (FSH), corticosteroid binding globulin (CBG), renin angiotensinogen, angiotensin-I and aldosterone levels between the two treatment regimens were noted. While both regimens were effective in reducing menopausal symptoms, none of the regimens could eliminate all symptoms completely. Treatment with Climen appeared to result in less frequent occurrences of some symptoms. During periods of no estrogen (only true for Climen) as well as periods of maximum P and E, subjects on Climen had significantly lower incidence of some of the symptoms (backache, lack of concentration, lethargy and swelling) when compared to those on Prempak-C.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

The impact of long-term testosterone replacement therapy on lipid and lipoprotein profiles in women.

The lipid and lipoprotein profiles of 39 female transsexuals, exposed to testosterone esters (250 mg monthly) for an average duration of 33 months after their sex reassignment operation (group 2), were compared to those of 29 normal menstruating female transsexuals prior to starting androgen therapy (group 1). A third group, comprising 17 post-operative female transsexuals were studied while on, and after stopping their androgen therapy for 6-12 months (group 3). The average concentration of testosterone in androgenized women was comparable to those found in normal males and levels of SHBG were significantly lower than those in the control group. No significant difference was noted between all levels of lipids and lipoproteins in pre-operative subjects of group 1 and corresponding levels in subjects of group 3 after they had stopped their androgen therapy for 6-12 months. Significantly higher levels of triglyceride (Trig), total cholesterol (TC), low-density lipoprotein (LDL-C) and apolipoprotein-B (Apo B) and a significantly lower level of high-density lipoprotein-cholesterol (HDL-C) were noted in androgenized women (group 2) when compared to controls (group 1). The two atherogenic indices, LDL-C/HDL-C and Apo-AI/Apo-B were significantly raised and lowered, respectively. Similar results were noted when comparing lipid and lipoprotein profiles in subjects of group 3 while they were on and after stopping their androgen therapy. Results from this study indicate that testosterone, per se, at supraphysiological doses may promote atherogenicity in women. Furthermore, the male predilection for coronary vascular diseases (CVD) may be due to the adverse effects of higher androgen levels on lipid and lipoprotein profiles.

Adult↗
PubMed1994

Endocrine effects in Asian postmenopausal women treated with SH D 461 M and Prempak-C.

We reported the results of a randomized cross-over study comparing SH D 461 M (Climen) and Prempak-C in 38 postmenopausal women who were established users of hormone replacement therapy (HRT). Climen contains 11 tablets of 2 mg estradiol valerate (EV), and 10 tablets with 2 mg EV plus 1 mg of cyproterone acetate. Prempak-C, on the other hand, is a regime consisting of 28 tablets of 0.625 mg conjugated equine estrogens (CEE); the last 12 tablets are taken together with 0.15 mg of norgestrel (NG) tablets. Patients in Sequence I started with Climen for 6 months and then crossed-over to Prempak-C, for the next 6 months; patients in Sequence II, followed the reverse order. Following Climen treatment, significantly higher levels (P < 0.05, t-test) of sex hormone binding globulin (SHBG) and estradiol, when compared to Prempak-C treated subjects, were noted. No significant differences in follicle stimulating hormone (FSH), corticosteroid binding globulin (CBG), renin, angiotensinogen, angiotensin-I and aldosterone levels between the two treatment regimes were noted. While both regimes were effective in reducing menopausal symptoms, none of the regimes could eliminate all symptoms completely. Treatment with Climen appeared to result in less frequent occurrences of some symptoms. During periods of no estrogen (only true for Climen) as well as periods of maximum progestagen and estrogen (P and E), subjects on Climen had significantly lower incidence of some of the symptoms (backache, lack of concentration, lethargy and swelling) when compared to those on Prempak-C.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Stimulation regimens in Assisted Reproductive Technology (ART) programme: experience in the University Hospital, Singapore.

Ovarian stimulation is critical to the success of patients in Assisted Reproductive Technology (ART) programmes. We compared two stimulation regimes retrospectively for ART in the NUH programme. These were the 2:1 and the GnRHa-FSH/hMG regimes. The former was our first-line regime while the latter was used for cycles where there was a prior endogenous LH surge, previous poor response, or an elevated LH level between days three to five of the cycle. All cycles in our ART programme in 1991 were studied, except those for special research procedures, e.g. micro-insemination sperm transfer (MIST) cycles, a total of 241 cycles. Cancellation rates were 14.4% (21 of 146 cycles) and 37.3% (19 of 51 cycles) for the 2:1 and GnRHa-FSH/hMG regimes respectively (p > 0.001). For the 2:1 regime, the majority of cancellations were due to ovulation prior to the oocyte recovery (42.9%; nine of 21 cycles). However, for the GnRHa-FSH/hMG regime, almost all the cancellations were due to poor response (84.2%; 16 of 19 cycles). Fertilisation rates were lower for the 2:1 regime (for both IVF-ER and IVF-TET, where sperm quality was poorer) compared to the GnRHa-FSH/hMG (55.0 and 66.6% respectively; p < 0.001). Pregnancy rates were higher for the 2:1 regime when IVF-ER and IVF-TET were used (16.4% and 23.3% respectively per oocyte recovery, versus 9.8% and 18.8% respectively for the GnRHa-FSH/hMG regime).

Drug Evaluation↗
PubMed1992

Effects of cross-gender steroid hormone treatment on prolactin concentrations in humans.

It is well known that peripheral prolactin levels are significantly higher in menarcheal women than in men. Higher levels of prolactin in menarcheal women are related to exposure to higher levels of estrogen in women than in men. Increased exposure to androgens in men has also been proposed as a possible reason to account for lower prolactin levels in men; however, this suggestion has not been conclusively proven. The current study sought to evaluate the cross-gender effects of male and female hormones on basal levels and the pituitary store of prolactin in humans. Four groups of individuals were involved: normal men and women, male and female transsexuals primed with female hormones and testosterone, respectively for at least 6 months. A metoclopramide challenge test was carried out on each subject of each group. Subjects were rested for 1 h, with an indwelling catheter in the antecubital vein, before a blood sample was collected for estimation of basal hormone levels. Following an oral ingestion of 10 mg of metoclopramide, blood samples were collected at 15, 30, 60, 90, 120, 150 and 180 min. Prolactin, estradiol and testosterone concentrations were measured by radioimmunoassay. Basal levels as well as metoclopramide-induced releases of prolactin (as measured by area under the curve) in normal women were significantly higher (p less than 0.05) than corresponding levels in normal men. Following long-term priming with female hormones, the pattern of response to metoclopramide in male transsexuals was dramatically changed.(ABSTRACT TRUNCATED AT 250 WORDS)

Estradiol↗
PubMed1992

Oogenesis, fertilisation and early embryonic development in rats. I: Dose-dependent effects of pregnant mare serum gonadotrophins.

Five hundred and eight mature female Wistar rats divided into 35 different groups were stimulated with pregnant mare serum gonadotrophins (PMSG) (0, 5, 10, 20 & 40 IU) at the late diestrus stage to induce multiple follicular development. No chorionic gonadotrophin (CG) was used for ovulation induction. The quality of oocytes and their in vitro fertilisability, quality of Day 2-embryos, viability of pregnancy and status of fetuses on Day 14 of gestation and status of embryos retrieved on Day 2, 3, 4 and 5 of pregnancy in different subgroups of rats were examined. Results showed that more oocytes and embryos fertilised in in vivo were retrieved from rats supraphysiologically stimulated with 20 IU of PMSG. However, concurrent with the larger number, higher proportions of abnormal oocytes and embryos were found. High doses of PMSG caused lower in vitro fertilisability of oocytes and greater degrees of embryonic degeneration. Although, the number of oocytes and Day 2-embryos were higher in the 20PMGS dose group, the pregnancy rate was significantly reduced to 27%. In the 40PMSG group no viable pregnancy was noted. Most embryo demise occurred by day 3-5 of pregnancy, probably within the oviducts and before the implantation stage. In rats supraphysiologically stimulated with 20 and 40 IU of PMSG, the number of morphologically normal looking embryos was greatly reduced by Day 3-5 of pregnancy. In the 40PMSG group, there were no embryos retrieved by Day 4 and 5.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Oogenesis, fertilisation and early embryonic development in rats. II: Dose-dependent effects of human chorionic gonadotrophin.

A total of 950 female Wistar rats in 81 groups were involved in this study. Different groups of rats were stimulated with PMSG (0, 10 & 20 IU) at diestrus followed, 48-52 hr later, by different doses of HCG (0, 10, 20, 30 & 40) for ovulation induction. The dose-dependent effects of HCG, either with or without the use of PMSG for stimulation of multiple follicular development, on the quality of oocytes and their in vitro fertilisability, quality of Day 2-embryos, viability of pregnancy and status of embryos retrieved on Day 2, 3, 4 or 5 of pregnancy in different subgroups of rats were examined. Results showed that more oocytes and embryos fertilised in vivo were retrieved from rats supraphysiologically stimulated with 20 IU of PMSG. The addition of HCG did not increase the number of ovulated oocytes or Day-2 embryos. In other words, the number of oocytes or embryos produced is dependent on the dose of PMSG administered during diestrus rather than on the dose of HCG given for ovulation induction. Hence, no increase in the amount of HCG is required to effectively ovulate bigger cohort of preovulatory follicles in supraphysiologically stimulated rats. As was shown earlier, in vitro and in vivo fertilisation rates were reduced when higher doses of PMSG were used. Similarly, these rates were reduced when increasing doses of HCG were used in rats not previously stimulated with PMSG. When higher doses of HCG were used in rats stimulated earlier with PMSG (10 and 20 IU), the in vitro but not the in vivo fertilisation rates were further reduced.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Long-term oestrogen priming on basal and oestradiol-induced release of luteinising hormone secretion in male rats.

The response of prolonged oestrogen priming (by silastic implants) of the male rat hypothalamic-pituitary axis (HPA) to an oestrogen challenge test was investigated. Basal LH levels were suppressed to a maximum at two months and remained unchanged by four months. In contrast to response in human, oestrogen priming had failed to stimulate a positive feedback response to an oestrogen challenge test in the male rats. Instead, oestrogen priming might have attenuated the negative LH feedback response. Increasing the dose of oestrogen priming by increasing the duration was not effective in inducing positive feedback in the male rats. The failure of these priming regimes to stimulate positive feedback in male rats may reaffirm our earlier suggestion that oestrogen does not play an important role in activating the cyclic centre in rats. This would also contradict the suggestion that testicular secretions may have acted through conversion to oestradiol in the suppression of the cyclic system in males during the critical period of differentiation of the HPA.

Animals↗
PubMed1991

Male endocrine functions in workers with moderate exposure to lead.

Evidence for the effect of occupational exposure to lead on the male endocrine system is conflicting. This study evaluated the primary (testicular) and secondary (hypothalamo pituitary testicular) effects of exposure to lead in 122 current lead workers and 49 non-exposed workers. The mean current blood lead concentration was 35.2 (range 9.6-77.4) micrograms/dl in the exposed workers, and 8.3 (range 2.6-14.8) micrograms/dl in the non-exposed workers. Concentrations of plasma luteinising hormone (LH) and follicle stimulating hormone (FSH) were both significantly higher in the exposed workers, but testosterone (T) was not significantly different between the two groups. In older exposed workers, however (greater than or equal to 40 years), plasma T concentrations were significantly lower, but LH and FSH concentrations were not significantly different. Compared with non-exposed workers, those exposed for less than 10 years had significantly raised LH and FSH and normal T concentrations whereas those exposed for 10 or more years had significantly lower T, and normal LH and FSH concentrations. The concentrations of LH and FSH showed a moderate increase in relation to blood lead concentrations in the range of 10 micrograms/dl to 40 micrograms/dl and thereafter reached a plateau or declined. No apparent trend for plasma T concentrations occurred. No significant difference in prolactin (PRL) concentration was noted. It is concluded that moderate exposure to lead was associated in dose related fashion with small but measurable changes in male endocrine functions that reflected both primary and secondary effects of lead on the testes and the hypothalamo pituitary testicular axis.

Adolescent↗
PubMed1990

Effect of estrogens on prolactin secretion in transsexual subjects.

The effect of estrogens on the secretion of prolactin in 8 different groups of transsexual subjects was studied. Two different types of estrogens, estradiol or its conjugate and ethinyl estradiol, were used. Different doses and durations of exposure were employed. Plasma levels of prolactin and SHBG after estrogen exposure were compared with corresponding levels before treatment. Results showed that for estrogens to exert an enhancing effect on the secretion of prolactin, three factors needed to be considered: (i) the absolute concentration of estrogen, (ii) the duration of exposure, and (iii) whether levels of SHBG are sufficiently altered to change the concentration of free estrogen. It appears that there exist both time and dose thresholds for effective enhancement of prolactin secretion by estrogen. Estradiol and its conjugate are more likely to induce hyperprolactinemia than ethinyl estradiol. The reduced effect of the latter is probably related to its ability to induce large and rapid increases in SHBG binding which probably results in unaltered free estrogen concentration. In the light of this study, treatment of male transsexuals with high doses of estradiol in its conjugate forms must be viewed with caution.

Adult↗
PubMed1990

Effects of estrogens, clomiphene and castration in a male transsexual with as compared to those without hypersecretion of gonadotropins.

A 24-year-old male-to-female transsexual with hypersecretion of gonadotropins was studied with regard to his recovery from sex steroid hormone treatment before his sex change operation and the effects of castration, clomiphene tests and estrogens on the hypersecretion of gonadotropins. Computer-assisted tomography and X-ray results indicated that the possibility that the hypersecretion of gonadotropins was not associated with a pituitary adenoma could not be ruled out. After a period of recovery from previous sex steroid hormone therapy, inappropriately high FSH and LH levels in the presence of normal male levels of testosterone and estradiol were found. The latter normal levels failed to suppress both the FSH and LH levels. From the clomiphene challenge tests carried out before and after the sex reassignment operation, the estradiol infusion studies and treatment with ethinyl estradiol after the sex reassignment operation, it appears that the hypersecretion of gonadotropins was responsive to the negative feedback effect of estrogens. However, the sensitivity, especially that of FSH, was very attenuated. Even after 23 weeks of ethinyl estradiol treatment FSH remained well above the upper limit for normal men. The results showed that before his sex change operation the hypersecretion of gonadotropins in the patient was probably under autonomous control. Testicular factors at normal male concentrations appear to have a minimal negative feedback effect on the hypersecretion of gonadotropins. However, hypersecretion of gonadotropins can be suppressed by prolonged exposure to estrogens.

Administration, Oral↗
PubMed1990

The gonadotrophin surge in humans: its mechanism and role in ovulatory function--a review.

The presence of the positive feedback by oestrogen resulting in the mid-cycle gonadotrophin surge in women distinguishes the female's feedback control of gonadotrophin secretion from that in males. The gonadotrophin surge is an event crucial for final oocyte maturation, ovulation and subsequently for corpus luteum function. In this article, the roles of oestrogen, progesterone and testosterone in the regulation of the gonadotrophin surge are reviewed. Evidences appear to support the suggestion that an oestradiol pulse of sufficient potency and lasting for an adequately long duration alone is sufficient to trigger off the LH surge. Progesterone has a biphasic effect on LH secretion, and although not required for the initiation of the LH surge, may play a role in maintaining the LH peak. Testosterone, on the other hand, does not modulate the LH surge mechanism in man. Dysfunction of the gonadotrophin surge mechanism may account for some forms of ovulatory disorders: amenorrhoea and in some cases of delayed or precocious puberty. In patients with polycystic ovary syndrome (PCOS), different degrees of dysfunction of the gonadotrophin surge mechanism have been shown.

Adolescent↗