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Biomedical subjects

J K Lu

Publications and source records attributed to J K Lu.

At least 73 records · Page 4Linked to original sources
PubMed1984

Effects of the (imBzl)D-His6, Des-Gly analog of GnRH on gonadotropin and estradiol secretion in normal women.

The acute gonadotropin and estradiol responses following single subcutaneous injections of 10, 50, 100 and 200 micrograms of [(imBzl)]D-His6,Pro9-NEt]-GnRH were compared to those after 100 micrograms of [D-Trp6, Pro9-NEt]-GnRH. The gonadotropin responses after 50-100 micrograms of the D-His analog of GnRH were equivalent to those following 100 micrograms of the D-Trp analog. The ovarian E2 response, a reflection of the total cumulative secretion of gonadotropins, was similar at 100 micrograms of each analog. The estradiol response paralleled the increasing gonadotropin response accompanying the graded doses of the D-His analog, indicating the lack of a direct inhibitory action of this GnRH agonist on the ovary. Assessment of both gonadotropin and estradiol responses appears to be satisfactory for assessing relative potency among GnRH agonistic analogs.

Adolescent↗
PubMed1984

Pituitary hormones during the menopausal hot flash.

Eighteen postmenopausal women with severe hot flashes had continuous recordings of finger temperature and skin resistance as objective indexes of flushing episodes, and serial measurements of anterior pituitary hormones as indirect indexes of hypothalamic neurotransmitter activity. Significant increases of growth hormone, adrenocorticotropic hormone (ACTH), and luteinizing hormone (LH) occurred with maximal concentrations at 30, five, and 15 minutes, respectively, after the onset of the skin temperature rises. No significant fluctuations of prolactin (PRL), thyroid-stimulating hormone (TSH), or follicle-stimulating hormone (FSH) were observed. The mean serum cortisol concentration increased 15 minutes after the hot flash, presumably consequent to the preceding elevation of ACTH. Pituitary ACTH release may be secondary to hypothalamic cooling, whereas increased growth hormone and LH output and the thermoregulatory adjustments comprising the flushing episodes are all consistent with cyclic episodes of increased hypothalamic norepinephrine activity.

Adrenocorticotropic Hormone↗
PubMed1983

Estrogen replacement therapy by transdermal estradiol administration.

To determine whether the nonoral administration of estradiol (E2) might provide physiologic replacement without alteration of hepatic function, 20 postmenopausal women were studied before and after 3 weeks of treatment with either E2-containing transdermal therapeutic systems or placebo. Twenty premenopausal women were also studied. With E2-containing systems, serum E2 and estrone levels were restored to the premenopausal range. Variable responses of the different biochemical and biologic markers of the actions of E2 were observed. The most sensitive marker was vaginal cytology, with the E2 dosage reverting the maturation index to premenopausal values. Hot flashes, measured objectively, were reduced in frequency but not abolished. Serum levels of follicle-stimulating hormone and luteinizing hormone were lowered but remained higher than the premenopausal range. No significant changes were noted in urinary calcium/creatinine and hydroxyproline/creatinine ratios, which were used as markers of bone resorption. With active systems, no significant changes were noted in the concentrations of the hepatic proteins renin substrate and thyroxine-binding globulin or in the binding capacities of cortisol-binding globulin and sex hormone-binding globulin. These results indicate that transdermal E2 administration may be used to provide estrogen replacement while exerting limited effects on hepatic function.

Calcium↗
PubMed1983

Gonadotropin secretion during prolonged hyperprolactinemia: basal secretion and the stimulatory feedback effect of estrogen.

Inoculation of cyclic female rats with the prolactin (Prl)/growth hormone-secreting pituitary tumor, MtT.W15, resulted in a cessation of estrous cyclicity within 5--10 days. Associated with this acyclicity was a persistently low serum concentration of estradiol and marked increases in both circulating Prl and progesterone. At Day 26 of acyclicity, basal serum luteinizing hormone (LH) values measured in samples taken every 20 min from 0900--1100 h were significantly reduced when compared to cyclic, nontumor animals on diestrus Day 2. There was no difference in basal follicle-stimulating hormone (FSH) concentrations. In a separate group of acyclic, tumor-bearing females 42--56 days after transplantation, a single s.c. injection of 20 micrograms estradiol benzoate (EB) at 1030 h elicited significant increases in both serum LH and FSH values between 1700 and 1830 h on the next day. The magnitude of the LH surge was reduced and that of FSH was increased in tumor-bearing animals when compared to cyclic, nontumor females given a similar EB injection on diestrus Day 1. These results demonstrate that chronic hyperprolactinemia is associated with inhibition of basal LH secretion and ovarian estrogen production and an increase in circulating progesterone concentrations. Nevertheless, the stimulatory feedback effects of estrogen on LH and FSH release are still present and functioning in acyclic female rats under chronically hyperprolactinemic conditions. These data suggest that the cessation of regular ovulatory cycles associated with hyperprolactinemia may be due to a deficiency of LH and/or estrogen secretion, but not to a lack of central nervous system response to the stimulatory feedback action of estrogen.

Animals↗
PubMed1983

Impermeability of the rat blood-brain barrier to exogenously administered gonadotropin-releasing hormone.

To assess the permeability of the blood-brain barrier (BBB) to exogenously administered gondatrophin-releasing hormone (GnRH), a study was performed in male-rats using the double isotope, intracarotid, single injection technique of Oldendorf. The mean (+/- SEM) brain uptake indices (BUI) of 3H-GnRH in comparison to a freely diffusible reference compound, 14C-butanol, were 1.1 +/- 0.2, 3.5 +/- 0.7 and 3.0 +/- 0.6 when the injection vehicles were Ringer's lactate, rat serum and human serum, respectively. The BUI of 3H-GnRH was similar to that of 3H-inulin, a nondiffusible compound. With different concentrations, the BUI of 3H-GnRH did not change significantly. These data indicate that the BBB of the male rat is impermeable to exogenously administered GnRH.

Animals↗
PubMed1983

Induction of hot flashes in premenopausal women treated with a long-acting GnRH agonist.

To examine the relationship between the occurrence of menopausal hot flashes and the pulsatile release of LH, we have investigated the serum hormone levels and the occurrence of hot flashes by objective recordings in five women with endometriosis given daily injections of a long-acting GnRH agonist (GnRH-a) for 28 days. Results were compared to the findings made in 25 young women 6-8 weeks after bilateral oophorectomy. Serum levels of estrone and estradiol were similar in the subjects given GnRH-a and the women who underwent a surgical castration. In comparison with values before GnRH-a administration, the mean FSH level was lower whereas the mean LH concentration was significantly higher (P less than 0.01) on the last day of therapy. The coefficients of variations of both gonadotropins measured during 4-h sampling periods at 20-min intervals before and at the end of GnRH-a administration were significantly reduced (P less than 0.01) with therapy. During the total of 20 h of frequent sampling in the 5 subjects, 15 pulses (20% rise from nadir) of LH and 12 pulses of FSH were detected before GnRH-a, whereas only 2 and 8 pulses, respectively, were observed on day 28 of treatment. Hot flashes were observed in both groups of patients. The proportion of women experiencing hot flashes, the rate of occurrence/h and the characteristics of the physiological changes were similar in the 2 groups of women. These data indicate that hot flashes can occur in the absence of prominent LH pulses, suggesting the pulsatile release of this hormone is merely associated with the hot flash rather than being etiological.

Castration↗
PubMed1983

HLA genotyping in family members and patients with familial polycystic ovarian disease.

To determine whether the familial occurrence of polycystic ovarian disease (PCO) is related to the major histocompatibility complex (HLA), four families in whom at least two siblings had clinical evidence of disease were examined. The diagnosis of PCO was confirmed by increased serum testosterone, androstenedione, and LH levels compared to those in normal women. Elevated concentrations of dehydroepiandrosterone sulfate indicated excess adrenal androgen secretion. The result of HLA genotyping in the families studied demonstrate that PCO does not exhibit linkage to the HLA system.

Androgens↗
PubMed1983

Steroid secretion in polycystic ovarian disease after ovarian suppression by a long-acting gonadotropin-releasing hormone agonist.

The principal glandular source of increased serum androgens in polycystic ovarian disease (PCO) is controversial), since complete separation of ovarian from adrenal function has not been achieved. The purpose of this study was to determine whether a long-acting GnRH agonist could be used to selectively inhibit ovarian steroid secretion in PCO and ovulatory women. Each of five typical PCO patients and six ovulatory subjects on day 2 of their menstrual cycles received D-Trp6-Pro9-NEt-LHRH (GnRH-a; 100 micrograms) for 28 consecutive days. Their results were compared to basal serum hormone values in eight oophorectomized women. In response to GnRH-a, PCO and normal subjects exhibited sharp and sustained rises of LH and gradual decreases in FSH. These levels were clearly less than basal levels seen in oophorectomized women. Episodic LH release was significantly attenuated in both groups at the end of GnRH-a treatment. After the administration of agonist, serum estradiol (E2), estrone (E1), androstenedione (A), and testosterone (T) were suppressed to castrate levels in both groups. The decrements of E2 and E1 in PCO were gradual and continuous compared to initial dramatic rises, which reached peaks at 14 days, and subsequent abrupt falls in the ovulatory controls. Serum A and T declined steadily in both groups. Basal serum dehydroepiandrosterone and dehydroepiandrosterone sulfate, but not cortisol, levels were elevated in PCO subjects. The 24-h secretion patterns and responses to ACTH of these hormones in PCO and ovulatory subjects were unaltered by GnRH-a administration. These data demonstrate that 1) in PCO subjects, GnRH-a induced complete suppression of ovarian steroid secretion, as circulating levels at the end of treatment were comparable to those seen in our oophorectomy subjects; 2) elevated A and T levels in PCO patients were derived primarily from the ovary; and 3) adrenal steroid secretion was unaltered by GnRH-a in both PCO and normal women.

Adrenal Cortex Hormones↗
PubMed1982

Silastic implants of progesterone produce high circulating levels of both progesterone and 20 alpha-hydroxyprogesterone in ovariectomized, adrenalectomized rats.

Previous studies indicated that circulating 20 alpha-hydroxyprogesterone (20 alpha-OH-P) in cyclic female rats derived from enzymatic conversion of progesterone in corpus luteum tissue (Hashimoto and Wiest, 1969). A possibility of extraovarian conversion of progesterone to 20 alpha-OH-P also was revealed by our recent finding that placement of Silastic implants of progesterone produced not only high plasma progesterone but also 20 alpha-OH-P in ovariectomized (OVX), previously pseudo-pregnant, rats (Gilman et al., 1981). This study was performed to measure the amounts of serum 20 alpha-OH-P and progesterone in intact or adrenalectomized (ADX), cyclic female rats and in OVX, ADX or OVX-ADX animals with or without progesterone implants. Twenty-four-hour patterns of serum progestins revealed that OVX rats exhibited low progesterone secretion (3-6 ng/ml) and undetectable levels of 20 alpha-OH-P in the absence of ovaries. In intact, cyclic females, circulating concentrations of 20 alpha-OH-P were 4- to 6-fold greater than those or progesterone. ADX resulted in a partial reduction of progesterone but not 20 alpha-OH-P in the circulation. Placement of 4 cm Silastic implants of progesterone produced high serum concentrations of both progesterone (29 +/- 4 ng/ml, mean +/- SEM) and 20 alpha-OH-P (27 +/- 1 ng/ml) in OVX and OVX-ADX rats. These findings demonstrate that placement of progesterone implants into female rats produces high circulating concentrations of both progesterone and 20 alpha-OH-P, and indicate that an extraovarian and extra-adrenal system(s) for progestin conversion is functioning under persistently high circulating progesterone conditions. By this system, large amounts of circulating progesterone are transformed into a less potent progestational compound, 20 alpha-OH-P.

Adrenalectomy↗
PubMed1982

Enhanced disparity of gonadotropin secretion by estrone in women with polycystic ovarian disease.

The disassociation between serum LH and FSH levels in polycystic ovarian disease (PCO) has been attributed to chronic acyclic estrogen production characterized by a predominance of circulating estrone (E1). This study was designed to determine whether the administration of estrone benzoate (E1B) modulates gonadotropin release in PCO. In five normal women studied during the early follicular phase of a control and subsequent treatment cycle, daily LH and FSH levels were unaltered by E1B administered from days 2 to 6. Gonadotropin responses to LRF given on day 7 were similar during control and treatment cycles. In seven patients with PCO, the mean LH concentration (25.7 +/- 0.7 mIU/ml) and the daily pattern of release were unchanged by E1B administered for 14 days. In contrast, a progressive decline in FSH occurred in each subject. Mean FSH levels decreased significantly from a pretreatment value of 11.3 +/- 0.2 to 9.3 +/- 0.9 mIU/ml by day 2 (P less than 0.05) and 7.2 +/- 1.2 mIU/ml by day 14 (P less than 0.005) of E1B administration. The LH response to LRF in PCO was significantly greater than that observed in the normal subjects, whereas responses before, during, and after E1B administration were similar. The FSH responses to LRF in PCO subjects were comparable to those of the normal subjects. These data indicate that the administration of E1B to PCO subjects reduces FSH levels without altering LH release, thereby enhancing the disparity of gonadotropin secretion encountered in this syndrome. This finding is consistent with the hypothesis that impairment of FSH release by chronic acyclic estrogen production derived from nonglandular aromatization of circulating androgen could in large part be responsible for anovulation in PCO.

Estradiol↗
PubMed1982

Biologic effects of various doses of ethinyl estradiol in postmenopausal women.

To determine which dosage of estrogen might provide physiologic replacement while minimizing adverse effects, 20 postmenopausal women were studied before and after oral administration of ethinyl estradiol. Twenty premenopausal women studied in the early and late follicular phases of the menstrual cycle were presumed to reflect normal physiologic function. Variable responses of the different biochemical and biologic markers to the actions of ethinyl estradiol were observed. Liver protein synthesis was the most sensitive measure of the action of ethinyl estradiol. In comparing the relative potencies of ethinyl estradiol with previously reported results observed with the usage of conjugated equine estrogens, the actions of 10 micrograms ethinyl estradiol were approximately equivalent to the biologic effects of 1.25 mg conjugated estrogens. The results suggest that ethinyl estradiol is far more potent than previously believed and that the daily administration of 10 micrograms, a dose lower than currently available commercial preparations, may be adequate for relief of symptoms of vaginal atrophy and may provide protection from the occurrence of osteoporotic fractures.

Administration, Oral↗
PubMed1981

Objectively recorded hot flushes in patients with pituitary insufficiency.

A study was conducted of 2 young adult women with pituitary insufficiency and complaints of hot flushes. Both underwent continuous recordings of skin temperature of the finger and skin resistance over the sternum as objective indices of flushing episodes. Frequent blood samples were also obtained during the recordings for the measurement of serum LH and FSH levels. During the 10 h of recording, 12 subjective hot flushes occurred and each was associated with a rise of finger temperature of greater than 1 C. Eighty-five percent of the temperature rises were associated with measurable decreases in skin resistance. The mean interval between flushes, the magnitude of the skin temperature and resistance changes, and the relationship of these changes to the onset of subjective flushes were identical to those observed in symptomatic postmenopausal women. Circulating gonadotropin levels were in the low to low normal range in comparison to values observed in premenopausal women and showed minimal pulsatile release. There were no significant correlations between finger temperature changes and LH levels in either subject. These results suggest that the previously described association of pulsatile LH release and the occurrence of hot flushes in postmenopausal women cannot be attributed to augmented LH secretion per se and, therefore, may be due to hypothalamic factors responsible for pulsatile LH release.

Adult↗
PubMedDate not supplied

Molecular characterization of tetralogy of fallot within Digeorge critical region of the chromosome 22.

The purpose of this study was to determine whether the levels of heterozygosity and microdeletion of specific loci within the DiGeorge critical region (del22q11) are associated with different phenotypes of tetralogy of Fallot (TF). Examinations were conducted on 84 sporadic TF patients and their unaffected parents for del22q11, using the following 9 simple tandem repeat polymorphic microsatellite markers: D22S420, D22S427, D22S941, D22S944, D22S264, D22S311, D22S425, D22S303, D22S257. The microdeletions were confirmed using quantitative PCR with markers TUPLE1, exon 2 of the UFD1L gene, and D22S264; the boundaries of these microdeletions were estimated using genotypic analyses of the unaffected family members. The del22q11 was identified in 14 patients (16.6%). The boundary of the shortest region of deletion overlap (SRO) in these 14 TF patients was identified, proximally using D22S427 and distally using the TUPLE 1 gene. The deletion of exon 2 of the UFD1L gene and TUPLE1 gene was identified in 13 patients (13/14 cases; 93%). The SRO in TF patients with del22q11 was at or close to the ADU breakpoint and centromeric to the UFD1L gene. The level of heterozygosity for the marker D22S944 in TF patients without del22q11 (n = 70) was found to be significantly lower than expected. Overall, this study demonstrated the significantly low level of heterozygosity within DiGeorge critical region in TF patients with or without del22q11. Our results suggest that the genetic factors leading to DiGeorge/velocardiofacial syndrome might also be partly responsible for TF phenotypes.

Adolescent↗