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Biomedical subjects

L M Demers

Publications and source records attributed to L M Demers.

At least 127 records · Page 7Linked to original sources
PubMed1989

The onset of sperm production in pubertal boys. Relationship to gonadotropin excretion.

To determine the relationship of gonadotropin excretion to spermarche, 26 boys ranging in age from 10.3 to 17.5 years each provided ten overnight urine samples. Microscopic observation of sperm was found in 33 (13%) of the 260 samples, with 50% of the boys exhibiting sperm in at least one specimen. No further cumulative gain in detecting spermaturia occurred after the seventh urine collection. The median age of spermarche was computed by logistic regression analysis to be 14 years. Three urine collections from each boy were assessed for gonadotropin levels. At age 14 years mean follicule-stimulating hormone and luteinizing hormone excretion were, respectively, 857 and 503 mIU/h, into the reported adult daytime range. Spermarche is a midpubertal event associated with age-appropriate gonadotropin production.

Adolescent↗
PubMed1988

Kinetic and morphometric responses of heterogeneous populations of experimental breast cancer cells in vivo.

Although the hormone responsiveness of some breast cancers is well known, the differential sensitivity of tumor cell subpopulations to hormonal effects is not well established. These experiments were designed to address this issue using the hormone-responsive N-nitrosomethylurea-induced rat mammary tumor. Rats bearing these tumors were randomly assigned to no treatment, 7-day castration, and 7-day castration followed by 1-, 3-, 7-, and 10-day treatment with estradiol benzoate (5 micrograms) and perphenazine (1 mg) to stimulate prolactin release. Under these conditions, the proportion of different cell populations was estimated with morphometric analysis, while their replicative activity was assessed using [3H]thymidine autoradiography. In tumors of intact rats the fractions of glandular epithelial, myoepithelial, and nonepithelial cells were 88.2%, 3.8%, and 8.0%, respectively. All cell types manifested a similar kinetic response to our hormonal treatments characterized by a drastic decline in the labeling index after castration followed by a progressive increase with hormone repletion which peaked on Day 7 of treatment. The magnitude of the response was, however, greater in the epithelial components of the tumor (glandular and myoepithelial cells), where the peak labeling indices significantly exceeded those observed in the tumors of control intact rats. Castration reduced the proportion of glandular cells while increasing the fractions of myoepithelial and nonepithelial cells. Furthermore, castration reduced the volume of the glandular-epithelial cells by 35%, which accounted for approximately half of the overall tumor volume reduction induced by ovariectomy. These alterations in tumor morphology were partially reversed by hormone repletion. These results underscore the exquisite hormonal sensitivity of different cellular counterparts of this experimental breast cancer with regard to both kinetic and morphological characteristics. They also provide support for stromal-epithelial interaction in the hormonal modulation of breast cancer growth.

Animals↗
PubMed1988

Determinants of peak trabecular bone density in women: the role of androgens, estrogen, and exercise.

To elucidate determinants of peak trabecular bone density, we studied the role of androgens, estrogen, and aerobic exercise in 30 women from 18 to 22 years old. The women were divided into three groups: Sedentary, 11 normal women who did not exercise regularly; eumenorrheic, 10 athletes with normal menstrual function; and oligomenorrheic, 9 athletes with exercise-induced oligomenorrhea. All athletes participated in aerobic sports that did not involve selective resistance loading of the back. Serum free and albumin-bound testosterone (fab T), androstenedione (A), and estradiol (E2) were measured on four separate occasions at consecutive 7 day intervals and averaged. Trabecular density was measured by quantitative computed tomography of the lumbar spine. Peak trabecular bone density was related to fab T (r = 0.48, p = 0.007), A (r = 0.40, p = 0.03), and E2 (r = 0.40, p = 0.04). When taken in combination, androgens and estrogen each accounted independently for significant portions of the variance in bone density [fab T and E2 (R2 = 0.38, p = 0.002) and A and E2 (R2 = 0.27, p = 0.01)]. Bone density (mg/ml, mean +/- standard error of the mean, SEM) in the sedentary group (174 +/- 6) was not significantly different from that in the eumenorrheic (183 +/- 12, p = 0.47) or oligomenorrheic (161 +/- 11, p = 0.32) subjects. We conclude that androgens and estrogen function as independent and additive determinants of peak trabecular bone density in young women. The quantitative impact of aerobic exercise (without resistance loading) and exercise-induced menstrual dysfunction appears to be less important than that of the hormones.

Adolescent↗
PubMed1988

Species-specificity of estradiol regulated growth factors in breast cancer.

Recent evidence indicates that autocrine/paracrine mechanisms may mediate the mitogenic effect of estradiol (E2) both in human and experimental breast cancer. However, the species-specificity of E2-regulated growth factors with regard to their biologic action has not been evaluated. To test this issue, we examined, in the soft agar clonogenic assay, the colony-stimulating activity in human breast cancers of conditioned media obtained from rat mammary carcinomas exposed to E2 (rat E2-CM). Of 22 primary human breast cancers plated in soft agar in the absence of serum, 18 (82%) successfully grew with a mean colony number of 62.4 +/- 9.8 (S.E.M.) (range 14-193). Rat E2-CM significantly stimulated colony formation in 10/18 (56%) human breast cancers to 155 +/- 11% (S.E.M.) of control. E2 administration (10(-9) M) in these tumors had a virtually identical overall effect (154 +/- 13% of control colony number). In the remaining eight tumors (44%), neither rat E2-CM nor E2 had, in general, a significant colony-stimulating effect. The growth-promoting action of rat E2-CM and E2 was not influenced by the hormone receptor status of the tumor. These results suggest that E2-regulated growth factors may not be species-specific, at least with regard to their colony-stimulating effects in soft agar.

Adult↗
PubMed1988

Transdermal testosterone therapy in the treatment of male hypogonadism.

Five hypogonadal men were treated with transdermal testosterone therapy, using a testosterone patch applied to the scrotal skin. Daily application of the patch, which contained 10 mg testosterone, produced an increase in serum testosterone concentrations from a pretreatment value of 45 +/- 12 (+/- SE; 1.5 +/- 0.4) to 436 +/- 80 ng/dL (15.1 +/- 2.8 nmol/L; P less than 0.001) after 4 weeks of treatment. Normal serum testosterone concentrations were achieved in all men after 6-8 weeks of therapy and were maintained during continued long term therapy for 9-12 months with a patch containing 15 mg testosterone. All men reported a subjective increase in libido and sexual function during therapy, and three men preferred it to testosterone injections. The serum testosterone and estradiol levels did not rise above the normal adult male range at any time during therapy. However, elevated serum dihydrotestosterone (DHT) concentrations occurred during treatment; the pretreatment DHT concentration was 95 +/- 3 ng/dL (3.3 +/- 0.1 nmol/L), and it increased to 228 +/- 40 ng/dL (7.8 +/- 1.4 nmol/L) after 4 weeks of treatment and remained elevated thereafter. The individual mean DHT to testosterone ratio increased from a pretreatment value of 0.2 (range, 0.1-0.3) to 0.6 (range, 0.4-0.7) after 2 weeks of therapy and remained high thereafter. Comparison of the serum DHT levels in patients during therapy with those in normal men who had similar testosterone concentrations [531 +/- 62 vs. 566 +/- 72 ng/dL (18.4 +/- 2.1 vs. 19.6 +/- 2.5 nmol/L); P greater than 0.05] revealed that the mean serum DHT concentration was significantly higher in the patients [315 +/- 69 vs. 87 +/- 6 ng/dL (10.8 +/- 2.4 vs. 2.9 +/- 0.2 nmol/L); P less than 0.001], as was the mean DHT to testosterone ratio [0.6 (range, 0.25- 1.1) vs. 0.16 (range, 0.09- 0.24); P less than 0.001]. The high serum DHT levels presumably were due to increased metabolism of testosterone to DHT by the 5 alpha-reductase in the scrotal skin. Serum 3 alpha-androstanediol glucuronide levels were not elevated in the patients. We conclude that transdermal testosterone therapy is an effective long term treatment for hypogonadism in men. It is, however, associated with high serum DHT levels, whose potential long term effects on the prostate and other tissues need to be investigated.

Administration, Cutaneous↗
PubMed1988

Effect of excess endogenous androgens on bone density in young women.

To determine whether endogenous androgens influence bone density in young women, we studied 27 normal women and 19 women with androgen excess, as defined by increased serum bioavailable testosterone (bio T) concentrations. The women ranged from 21-48 yr of age. The 2 groups were comparable with respect to age, anthropomorphic measures, nutrition, gynecological history, and serum cortisol and estradiol levels. Trabecular (lumbar) and cortical (radial) bone density were quantitated by computerized tomography and single photon absorptiometry, respectively. Serum obtained during the follicular phase of the cycle was assayed for bio T, total T, dehydroepiandrosterone sulfate, androstenedione (Adione), and 3 alpha-androstanediol glucuronide (3-Adiol-G). Trabecular bone density was significantly higher in the androgen excess group [172 +/- 7 (+/- SE) vs. 153 +/- 5 mg/mL; P = 0.03]; controlling for serum Adione (but not for serum bio T, total T, dehydroepiandrosterone sulfate, or 3 alpha-androstanediol glucuronide, or 3-Adiol-G) abolished this difference. Similarly, serum Adione correlated more strongly than the other androgens with trabecular bone density (r = 0.31; P = 0.03). Average cortical bone density was not higher in the androgen excess group (0.740 +/- 0.014 vs. 0.722 +/- 0.008 g/cm2; P = 0.27). Among the 27 normal women, cortical density was correlated to serum bio T (r = 0.47; P = 0.01) and total T (r = 0.53; P = 0.004), but not to the other androgens. We conclude that supraphysiological levels of endogenous androgens are associated with increased trabecular bone density in young women. Serum Adione appeared to be the best marker for the impact of androgen on trabecular density. Among normal women, cortical bone density was related to serum T.

Adult↗
PubMed1988

Correlation of serum 3 alpha-androstanediol glucuronide with acne and chest hair density in men.

Serum 3 alpha-androstanediol glucuronide (3 alpha-Adiol-G) is considered to be an indicator of peripheral tissue androgen metabolism. Precursor circulating androgens are converted in peripheral tissue to dihydrotestosterone (DHT), which is ultimately metabolized to 3 alpha-Adiol-G and secreted from the cell. Elevated serum 3 alpha-Adiol-G concentrations have been reported in women in hyperandrogenic states. We studied 44 consecutive male medical students for chest hair density, acne, and serum dehydroepiandrosterone sulfate (DHEA-S), total testosterone (total T), free and albumin-bound (bioavailable) T (bio T), and 3 alpha-Adiol-G concentrations. Although there was considerable overlap of serum 3 alpha-Adiol-G values among the groups defined by hair density or acne scores, we found statistically significant correlations between serum 3 alpha-Adiol-G and chest hairiness (P = 0.0034), acne (P = 0.0005), and a combined chest hairiness and acne score (P = 0.0018). There was no significant correlation between these clinical parameters and the levels of precursor androgens. There was, however, a strong correlation between serum 3 alpha-Adiol-G and bio T (P = 0.0005), suggesting that in men serum 3 alpha-Adiol-G levels may be dependent upon available free and albumin-bound T. The correlations in men of serum 3 alpha-Adiol-G with chest hair density, acne, and the hairiness and acne index supports the hypothesis that the serum levels of 3 alpha-Adiol-G reflect the extent of androgen action in peripheral tissues.

Acne Vulgaris↗
PubMed1988

Effect of isotretinoin on serum levels of precursor and peripherally derived androgens in patients with acne.

Sebaceous glands are stimulated by androgens and can convert them to more active forms. Isotretinoin, however, has a profound inhibitory effect on sebaceous gland size and function. This study evaluated the effect of isotretinoin on serum levels of precursor and tissue-derived androgens. Twenty-four subjects (15 men and nine women) were treated for 20 weeks with 1 mg/kg/d of isotretinoin. Serum samples were obtained at baseline, 8, 16, and 24 weeks, and assayed for precursor androgens--total testosterone (TT), free testosterone (free T), dehydroepiandrosterone (DHEA), dehydroepiandrosterone-sulfate (DHEA-S); and tissue androgens--dihydrotestosterone (DHT), and its metabolite, 3 alpha-androstanediol glucuronide (3 alpha-diol G). Isotretinoin had no meaningful effects on precursor androgens, except for producing an elevation of free T in women. In contrast, isotretinoin produced depressions in the serum levels of DHT and 3 alpha-diol G in women and in 3 alpha-diol G in men. These decreases are believed to be the result, rather than the cause, of a reduction in the size of the sebaceous glands: The magnitude of the observed decreases may represent the amount of tissue-derived androgens that sebaceous glands normally contribute to the circulating pool.

Acne Vulgaris↗
PubMed1988

Collegiate women athletes with irregular menses during adolescence have decreased bone density.

We studied six eumenorrheic and 13 oligomenorrheic collegiate women athletes who were matched in all respects other than menstrual histories. There was a significant (P less than .05) association between menstrual regularity and bone density. The severely oligomenorrheic subjects had modestly decreased plasma estrogen levels. These findings support the notion that plasma estrogen levels during adolescence play a significant role in the development of peak adult bone density in women.

Adolescent↗
PubMed1987

Effects of progestins on growth of experimental breast cancer in culture: interaction with estradiol and prolactin and involvement of the polyamine pathway.

The role of progesterone either alone or in combination with other hormones in breast cancer growth is not well established. In these experiments, using the hormone-responsive N-nitrosomethylurea-induced rat mammary tumor grown in the soft agar clonogenic assay, we tested the colony-stimulating effect of progesterone and the synthetic progestin R5020 over a wide range of physiological and pharmacological concentrations (from 0.1 nM to 10 microM). Both progesterone and R5020 were found to have a significant colony-stimulating effect which was more pronounced in the absence of serum. The action of progesterone appeared to plateau at concentrations of 10 or 100 nM, whereas R5020 was maximally effective at lower concentrations (approximately 1 nM). A biphasic dose-dependent effect was occasionally seen both with progesterone and R5020 with a loss of colony-stimulating effect at high concentrations. The combined administration of varying doses of progesterone (0.1, 1, 10, and 100 nM) and estradiol (10(-10) M and 10(-9) M) was found at times to potentiate and at times to decrease colony formation over that observed with the individual treatments. The former effect, when present, was usually seen with low doses of progesterone, while the latter was frequently observed with high concentrations (100 nM). No major potentiation or suppression of colony formation over individual treatments was observed when varying doses of progesterone (1, 10, and 100 nM) were added together with prolactin (50 ng/ml). The administration of the polyamine biosynthesis inhibitor alpha-difluoromethylornithine completely blocked the colony-stimulating effect of progesterone. The inhibitory effect of alpha-difluoromethylornithine was completely reversed in a dose-dependent fashion by exogenous administration of spermidine, thus implying a critical involvement of the polyamine pathway in progesterone action.

Animals↗
PubMed1987

Differing effects of fetal sex on pregnancy and its outcome.

An analysis of 52,198 pregnancies was undertaken to determine if male and female fetuses had differing environmental effects on their mothers. Early gestational blood pressure and weight gain were significantly higher in preeclamptic women with male than with female fetuses. Preeclamptic women had lower third trimester hemoglobin values and less frequent proteinuria with male than with female fetuses. Excessive syncytial knots, a characteristic placental consequence of low uteroplacental blood flow, were seen less frequently with male than with female fetuses. These findings are hypothesized to be due to a greater maternal blood plasma volume expansion with male than with female fetuses in preeclamptic pregnancies.

Blood Volume↗
PubMed1987

Polyamines and the synthesis of estradiol-regulated growth factors in rat mammary cancer in culture.

We have recently provided evidence to suggest that the polyamine pathway plays an essential role in the expression of the growth-promoting effect of estradiol (E2) regulated growth factors in the N-nitrosomethylurea (NMU) induced rat mammary tumor cultured in vitro in the soft agar clonogenic assay. To further explore the interaction between the polyamine pathway and autocrine control of tumor growth by E2, we tested whether, in our system, polyamines play a role in the synthesis of E2-regulated growth factors. Conditioned medium (CM) obtained from tumors treated with E2 and the polyamine biosynthesis inhibitor alpha-difluoromethyl-ornithine (DFMO) (1 mM) no longer exhibited the colony-stimulating effect which was consistently observed with E2-CM. Such growth promoting activity was restored in a dose-dependent fashion with CM obtained from tumors treated with E2, DFMO, and increasing concentrations of spermidine (from 1 to 100 microM). Conditioned medium obtained from tumors treated with DFMO with and without spermidine in the absence of E2 had no discernible effects on colony formation. The colony stimulating effect of the CM employed could not be accounted for by the contaminating presence in the media of E2, DFMO, or polyamines. These results indicate that, in our system, the polyamine pathway plays an important role in the synthesis of E2-regulated growth factors.

Animals↗
PubMed1987

Activation of protein kinase C is coupled to prostaglandin E2 synthesis in swine granulosa cells.

We have examined the role of phospholipid-sensitive calcium-dependent protein kinase (protein kinase C) in prostaglandin E2 synthesis by monolayer cultures of swine granulosa cells. Specific phorbol ester derivatives known to activate protein kinase C significantly augmented the production of prostaglandin E2. These stimulatory actions were dose and time-dependent, and could be abolished by the cyclooxygenase inhibitor, indomethacin, or the protein synthesis inhibitor, cycloheximide. Moreover, the rank order of potency of phorbol esters in enhancing prostaglandin E2 production was concordant with that demonstrated for activation of protein kinase C. Phorbol ester in conjunction with the divalent cation ionophore, A23187, increased prostaglandin E2 production synergistically. In addition, a non-phorbol stimulator of protein kinase C, 1-octanoyl-2-acetylglycerol, also significantly enhanced prostaglandin E2 biosynthesis. The stimulated synthesis of prostaglandin E2 was confirmed by high-pressure liquid chromatographic purification of this radiolabeled metabolite of 3H-arachidonic acid, and by capillary gas chromatography high-resolution mass spectrometry. Thus, the present studies indicate that the protein kinase C effector pathway is functionally coupled to prostaglandin E2 production in the swine granulosa cell.

Animals↗
PubMed1987

Peripheral prostaglandin metabolite levels in women undergoing therapeutic abortions in the first trimester with and without treatment with prostaglandin synthetase inhibitor.

The levels of 11-deoxy-13,14-dihydro-15-keto-11 beta, 16 xi-cyclo prostaglandin E2 (bicyclo PGEM), 13,14-dihydro-15 keto-prostaglandin F2 alpha (PGFM) and prolactin were measured in four serial plasma samples collected from thirty women undergoing therapeutic abortions in the first trimester by a suction curettage procedure. Eleven of these women received a preoperative loading dose of sodium meclofenamate, a PG synthetase inhibitor, before the abortion procedure was started and the rest received this medication after the last blood samples were drawn. Prolactin levels increased significantly during the procedure. Sodium meclofenamate treatment had no effect on this increase. Bicyclo PGEM levels did not increase during the procedure in untreated or treated women, whereas PGFM levels increased but only in untreated women. The lack of increase in treated women apparently was not a treatment effect because PGFM levels in corresponding samples of untreated and treated women were similar. Treatment significantly reduced the bicyclo PGEM levels immediately after completion of the procedure as compared to untreated women. This differential PG response to treatment is unprecedented and may be due to sodium meclofenamate inhibition of PGE2 and not PGF2 alpha synthesis. Nevertheless, these data demonstrate that sodium meclofenamate treatment of patients undergoing first trimester therapeutic abortion to relieve pain involves selective suppression of PGE2 synthesis.

Abortion, Therapeutic↗
PubMed1987

Activation of protein kinase C is coupled to prostaglandin F2 alpha synthesis in the ovary: studies in cultured swine granulosa cells.

We have investigated the role of phospholipid-sensitive calcium-dependent protein kinase (protein kinase C) in prostaglandin F2 alpha synthesis by monolayer cultures of swine granulosa cells. In this system, specific phorbol ester derivatives known to activate protein kinase C significantly augmented the production of prostaglandin F2 alpha. Phorbol ester in conjunction with the ionophore A23187 synergistically increased prostaglandin F2 alpha production. These stimulatory actions were dose- and time-dependent, and could be abolished by the cyclooxygenase inhibitor, indomethacin, or the protein synthesis inhibitor, cycloheximide. Moreover, the rank order of potency of phorbol esters in enhancing prostaglandin F2 alpha production was concordant with that demonstrated for activation of protein kinase C in the swine ovary. In addition, a nonphorbol stimulator of protein kinase C, 1-octanoyl-2-acetylglycerol, also significantly enhanced prostaglandin F2 alpha biosynthesis. The synthesis of immunoassayable prostaglandin F2 alpha was confirmed by high-pressure liquid chromatographic purification of this radiolabeled metabolite of [3H]arachidonic acid. Thus, the present studies indicate that the protein kinase C effector pathway in the swine granulosa cell is functionally coupled to prostaglandin F2 alpha production.

Animals↗
PubMed1987

Adrenal androgens, sex-hormone binding globulin and bone density in osteoporotic menopausal women: is there a relationship?

The relationships among sex steroids, sex hormone binding globulin (SHBG) and vertebral bone density as measured by computerized tomography were studied in 18 post-menopausal women. A significant negative correlation was found between SHBG binding capacity (SHBG-BC) and bone density. Bone density and the adrenal androgen dehydroepiandrosterone sulfate (DHEAS) declined with age, and SHBG-BC was correlated significantly with DHEAS concentrations. The relationship between SHBG-BC and bone density may be affected by adrenal androgen output.

Adrenal Cortex Hormones↗
PubMed1987

Declining adrenal androgens: an association with bone loss in aging women.

Bone loss in aging women is a major contributing factor to the onset of osteoporosis. To determine whether a decline in adrenal androgen output might be important in the loss of bone with age, we studied a highly selected group of 14 women, average age 70, and measured adrenal androgens in relationship to trabecular bone density. Dehydroepiandrosterone sulfate (DHEAS) levels were used as a marker of adrenal sex steroid output while quantitative, computerized tomography was used to determine trabecular bone density. Our results showed that both bone density (r = -0.69, P less than 0.01) and DHEAS levels (r = -0.68, P less than 0.01) declined with age, and that DHEAS was positively correlated with bone density (r = 0.66, P = 0.01). These data emphasize the association of declining adrenal sex steroid production with declining bone density during the process of aging.

Adrenal Cortex↗