Biomedical subjects

D W Killinger

Publications and source records attributed to D W Killinger.

At least 19 recordsLinked to original sources

PubMed1991

Null cell adenoma of the pituitary with features of plurihormonality and plurimorphous differentiation.

The case of a 35-year-old man with pituitary macroadenoma who was complaining of reduced sexual activity is presented. Histologic examination showed a chromophobic adenoma corresponding mainly to a null cell adenoma at the ultrastructural level. Focal plurihormonality and plurimorphous differentiation of adenoma cells were demonstrated by immunohistochemical and electron-microscopic studies. It is suggested that adenomatous null cells represent pluripotent progenitor cells capable of transforming to different hormone-producing cell types. The factors accounting for differentiating to various cell populations have yet to be elucidated.

Adenoma↗

PubMed1990

Influence of adipose tissue distribution on the biological activity of androgens.

To establish whether the conversion of androstenedione (A) to estrogens and 5 alpha-reduced metabolites in human adipose tissue was determined by the site of origin of the tissue, studies were carried out on adipose stromal cells from different body sites. Adipose tissue was obtained from the breast, omentum, abdomen, lower thigh, upper thigh, buttock, and flank from patients undergoing liposuction for cosmetic reasons or at surgery. Stromal cells were isolated after incubation of the adipose tissue with collagenase and were grown in culture using alpha-minimal essential medium (MEM) + 15% fetal calf serum. Studies of A metabolism were carried out when the cells were between days 4 and 12 in culture. After an 8-hour incubation with (3H)-A as substrate, estrone (E1), testosterone (T), 5 alpha-androstanedione (5 alpha-A-dione), androsterone (AND), and dihydrotestosterone (DHT) were isolated using thin layer and paper chromatography. The conversion per 1 x 10(6) cells of A of E1 was more than 10-fold greater in the upper thigh, buttock, and flank than in the breast, lower thigh, abdomen, or omentum (0.13-3.0 vs 0.01-0.09%). The formation of 5 alpha-reduced androgens varied from 0.86-10% and was similar in tissue from different body sites. Cortisol (10(-7) M) stimulated E1 formation 3- to 10-fold in cells from all sites, whereas 5 alpha-reductase activity was either unchanged or increased moderately (up to twofold). In cells from the abdomen, omentum, and lower thigh, the formation of 5 alpha-reduced androgens was more than 10-fold greater than the formation of E1. In cells from the upper thigh, buttock, and flank, E1 formation was comparable to 5 alpha-reduced androgen formation. These studies show marked differences in the relative conversion of A to estrogens and 5 alpha-reduced androgens in adipose stromal cells depending on their site of origin, and they suggest that the distribution of body fat may be a major factor in determining the biologic effects of secreted androgens.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

PubMed1989

Impaired spermatogenesis is not an obligate expression of receptor-defective androgen resistance.

We are studying a man who presented at age 21 years with severe extragenital subvirilization despite high-normal to above-normal levels of plasma testosterone for at least 5 years. At puberty, his penis, scrotum, and testes matured normally, and he did not develop gynecomastia; however, his voice, muscularity, and facial, sexual, and body hair remained immature. A 2.5-ml ejaculate yielded normal results for sperm density, morphology, and motility. Because persistent undervirilization was emotionally disabling, he has received pharmacologic doses of testosterone enanthate intramuscularly for 3.5 years. The treatment has improved his virilization and masculine self-image substantially, and his semen analysis has remained well within the normal range. The androgen receptor in his genital skin fibroblasts has a distinctively mutant phenotype: it has a low affinity (increased apparent equilibrium dissociation constant, Kd) for 5 alpha-dihydrotestosterone and two synthetic androgens, mibolerone (MB) and methyltrienolone (MT), and its binding capacity (Bmax) is normal for the other two ligands, but questionably low for MT. In addition, it up-regulates its activity normally in response to prolonged incubation with androgen, and its androgen-receptor complexes are not thermolabile. Our study of this man permits two conclusions: impaired spermatogenesis is not the irreducible expression of receptor-defective androgen resistance in man; and androgen pharmacotherapy may be remedial for those in whom extragenital subvirilization is emotionally costly and subnormal spermatogenesis is not an inevitable side effect of such therapy.

Adult↗

PubMed1989

Silent somatotroph adenomas of the human pituitary. A morphologic study of three cases including immunocytochemistry, electron microscopy, in vitro examination, and in situ hybridization.

Pituitary adenomas, removed surgically from three women with normal or slightly elevated serum growth hormone levels and no evidence of acromegaly, were studied. The tumor cells were shown by electron microscopy to correspond to sparsely granulated somatotrophs but immunocytochemistry showed that they contained no, moderate, or little growth hormone. Two tumors examined in vitro secreted small amounts of growth hormone in the tissue culture medium initially with a spontaneous rise after several days, and responded to growth hormone-releasing hormone stimulation with increased growth hormone release. In situ hybridization demonstrated growth hormone mRNA expression in adenoma cells. Clinically silent somatotroph adenomas represent a hitherto undescribed entity; electron microscopy shows that they consist of somatotrophs, and express growth hormone mRNA but do not secrete growth hormone in amounts needed to raise substantially serum growth hormone levels and cause acromegaly. Further work is required to clarify the mechanisms accounting for the lack of clinical and biochemical evidence of hormone excess associated with these tumors.

Adenoma↗

PubMed1988

Steroid modulation of aromatase activity in human cultured breast carcinoma cells.

Cortisol and steroids with progestational or androgenic activity were studied to determine the effects of these steroids on the conversion of androstenedione (A) to estrone (E1) in human cultured breast carcinoma cells. Cortisol (10(-6) M) stimulated aromatase activity in two estrogen unresponsive cell lines (MD, DM) and in an estrogen responsive cell line (MCF7) with the maximum stimulation occurring during confluence. Cortisol inhibited the replication of MCF7 cells but not MD and DM. Dihydrotestosterone, androsterone and 5 alpha-androstanedione (10(-6) M) inhibited the conversion of A to E1 by greater than 90% under basal and cortisol stimulated conditions. Progesterone (10(-6) M) had no effect on aromatase activity while the progestational agent R5020 (10(-6) M) produced a 30% inhibition. The anabolic steroids 19-nortestosterone and 19-norandrostenedione which also have progestational activity inhibited the conversion of A to E1 in a dose dependent manner with 90% inhibition at 10(-6) M. Danazol (10(-6) M) a drug with both androgenic and progestational activity inhibited E1 formation by 30%. Under the same conditions, the known inhibitor of aromatase, 4-hydroxyandrostenedione (10(-6) M) decreased E1 formation by more than 90% and aminoglutethimide (10(-6) M) caused only 25% inhibition. These studies demonstrate that endogenous and exogenous steroids may have significant effects in modulating the local formation of estrogens from androgen precursors in cultured breast carcinoma cells. This effect on estrogen formation may be a factor in the biological response of breast tissue.

Androstenedione↗

PubMed1988

A novel type of pituitary adenoma: morphological features and clinical correlations.

Twenty patients with a novel, frequently aggressive type of pituitary adenoma, termed silent subtype 3 adenoma on the basis of fine structural criteria, are reported. The surgically removed tumors were studied by morphological techniques, and the findings were correlated with clinical and biochemical data. All tumors were macroadenomas, often with parasellar extension. The histologically diffuse tumors frequently exhibited focal immunopositivity for one or more adenohypophysial hormones, although the majority of adenoma cells were negative. The tumors had characteristic electron microscopic features, assuring specific diagnosis and delineating this tumor type as a distinct ultrastructural entity. The tumors were removed from 9 women and 11 men (median ages, 27 and 41 yr, respectively). In all women, mild to moderate hyperprolactinemia and its sequelae were present from the early phase of the disease, leading to the erroneous diagnosis of prolactinoma. Bromocriptine therapy (3 patients) reduced serum PRL levels to normal, but failed to halt tumor growth. In men, most adenomas were nonfunctioning; 4 men had mild to moderate hyperprolactinemia. Three men had elevated serum GH levels and acromegaly, suggestive of multidirectional differentiation. Although the putative cell type giving rise to silent subtype 3 adenomas is not known, the tumor should be recognized to avoid erroneous diagnosis and inappropriate treatment.

Adenoma↗

PubMed1988

Structure-function correlations of human pituitary gonadotroph adenomas in vitro.

Two pituitary gonadotroph adenomas were studied in vitro to characterize structure-function correlations. Both tumors were from men, aged 63 and 69 years, who had elevated blood levels of follicle-stimulating hormone (FSH) and normal blood luteinizing hormone (LH) and testosterone values. The surgically resected adenomas contained diffuse immunohistochemical positivity for beta-FSH, beta-LH, and alpha-subunit of glycoprotein hormones; by electron microscopy they were composed of well-differentiated gonadotrophs. In vitro, both tumors released FSH, LH, and alpha-subunit. Morphometric studies were performed on surgically resected and cultured adenoma cells. Compared with the surgical specimens, the cultured cells had decreased cytoplasmic volume densities of endoplasmic reticulum and Golgi apparatus and slightly increased cytoplasmic volume densities of secretory granules. Incubation with gonadotropin-releasing hormone (GnRH) for 2 and 24 hours increased FSH, LH, and alpha-subunit release by both tumors; morphometry after 2 consecutive days of exposure confirmed significant increases in cytoplasmic volume densities of endoplasmic reticulum and Golgi regions and marked decreases in that of secretory granules. There was no significant change in cell size, nuclear/cytoplasmic ratio, or secretory granule diameter. The two tumors differed in their response to gonadal steroids. Estradiol, testosterone, and progesterone stimulated release of FSH, LH, and alpha-subunit by one tumor and the morphologic changes paralleled the biochemical response; addition of testosterone suppressed the secretory and morphologic response to GnRH. The other tumor showed no significant response to estradiol or testosterone and addition of these steroids did not alter the response to GnRH. The results are consistent with the interpretation that GnRH stimulates not only release but also synthesis of gonadotropins by gonadotroph adenomas of men. The data also indicate variable sensitivity of these tumors to gonadal steroids with paradoxical stimulation alone and inhibition of response to GnRH. The structural changes correlate with the hormone release response in vitro.

Adenoma↗

PubMed1986

Mammosomatotroph adenoma of the pituitary associated with gigantism and hyperprolactinemia. A morphological study including immunoelectron microscopy.

A 29-year old giantess with growth hormone excess and hyperprolactinemia underwent transsphenoidal surgery to remove her pituitary tumor. Electron microscopy revealed a mammosomatotroph adenoma composed of one cell type. Immunoelectron microscopy, using the immunogold technique, demonstrated predominantly growth hormone or prolactin or a varying mixture of both growth hormone and prolactin in the adenoma cells. The presence of growth hormone and prolactin was found not only in the cytoplasm of the same adenoma cells but also in the same secretory granules. In the nontumorous adenohypophysis, somatotrophs and lactotrophs showed ultrastructural signs of hyperactivity. This finding is in contrast with the presence of suppressed somatotrophs and lactotrophs seen in nontumorous portions of adult pituitaries harboring growth hormone or prolactin-secreting adenomas. Our morphological study reinforces the view that growth hormone-producing pituitary tumors, originating in childhood, are different from those of the adult gland.

Adenoma↗

PubMed1986

Ligand-specific thermal misbehavior of synthetic androgen-receptor complexes in genital skin fibroblasts of subjects with familial ligand-sensitive androgen resistance.

We have used 5 alpha-dihydrotestosterone (DHT) and two synthetic, non-metabolizable androgens, methyltrienolone (MT) and mibolerone (MB), to study intact genital skin fibroblasts from four subjects with familial incomplete androgen resistance. In each, the free androgen receptor has normal binding capacity at 37 degrees C and normal half-lives at 37-43 degrees C. In three the mutant receptor misbehaves in a pattern that is ligand-specific and temperature-dependent. At 37 degrees C the equilibrium (Kd) and non-equilibrium (k) dissociation constants, and the ability to augment binding activity during prolonged exposure to androgen, are impaired with DHT, but not with MT; with MB, only the k is abnormal. Mutant MT-receptor complexes dissociate normally even at 42 degrees C; yet, in cells post-incubated at 42 degrees C with cycloheximide and a saturating concentration of ligand, their pool size decays in the rank order, MT greater than MB greater than normal. This measure of lability is nonlinear as a semilogarithmic function of time; it varies directly with temperature and the concentration of cycloheximide, but inversely with that of ligand. Thus, MT and MB evoke distinct forms of thermal dysfunction from the androgen receptor in ligand-sensitive androgen resistance. This observation will help to elucidate the combinatorial properties of normal androgen-receptor complexes that enable them to regulate gene transcription differentially in various androgen target tissues.

Androgens↗

PubMed1986

The formation of 5 alpha-reduced androgens in stromal cells from human breast adipose tissue.

The present study was designed to determine if stromal cells derived from human breast adipose tissue contain 5 alpha-reductase activity, and to study the effect of 5 alpha-reduced androgens on aromatase activity under basal and cortisol stimulated conditions. Stromal cells were prepared from breast adipose tissue obtained at the time of surgery from four patients. The cells were isolated after collagenase digestion and were cultured in alpha-minimum essential medium with 15% fetal calf serum. Studies were carried out between days 4 and 11 of the third subculture in the presence or absence of cortisol (10(-6) M). Metabolism of androstenedione (A) was studied over a period of 8 h after addition of medium containing 20 X 10(6) dpm (100 pM) [3H]A. The cells metabolized A to estrone (E1), testosterone (T), 5 alpha-androstane 3, 17-dione (5 alpha-A-dione), androsterone (AND), and dihydrotestosterone. On day 7 of culture, product formation expressed as percent conversion of A per 1 X 10(6) cells ranged as follows: E1, 0.02-0.13; T, 0.12-0.36; 5 alpha-A-dione, 2.05-9.91; and a fraction containing AND and dihydrotestosterone, 0.38-0.59. In the presence of cortisol the rate of cell growth was decreased by 25% to 50%. The formation of E1 increased 150- to 1500-fold and AND formation increased 2- to 8-fold. There was no consistent change in the formation of 5 alpha-A-dione and T. The addition of 5 alpha-A-dione (10(-6) M) to the culture medium at the time of assay resulted in greater than 90% inhibition of E1 formation under both basal and cortisol stimulated conditions. The studies indicate that adipose tissue is an important site for the formation of 5 alpha-reduced androgens.

Adipose Tissue↗

PubMed1985

The relationship between growth and androstenedione metabolism in four cell lines of human breast carcinoma cells in culture.

The conversion of androstenedione (A) to estrogens, testosterone (T) and 5 alpha-reduced metabolites was studied in different phases of cell growth in 4 lines of cultured human breast carcinoma cells. Aromatase activity was 10-fold greater in MD and DM than in MCF7 cells and was undetectable in ZR75 cells. Estrogen formation in MD and DM lines increased during the phase of exponential growth and decreased to 20% of maximum during confluence. 5 alpha-Reductase activity was determined by the formation of 5 alpha-androstane-3,17-dione (5 alpha-A-dione) and androsterone (AND), and was 5-fold greater in ZR75 cells than MD cells and 2-fold greater than in MCF7 cells. This activity was relatively constant during exponential growth and decreased during confluence. T accumulation was inversely related to 5 alpha-reductase activity. The MCF7 and ZR75 cells which contain estrogen receptors had the highest levels of 5 alpha-reductase activity while the MD line which lacks estrogen receptors had the lowest 5 alpha-reductase activity. The assessment of aromatase and 5 alpha-reductase activity in addition to estrogen and progesterone receptors may be helpful in predicting hormone sensitivity in human breast tumours.

17-Hydroxysteroid Dehydrogenases↗

PubMed1984

The intracellular control of aromatase activity by 5 alpha-reduced androgens in human breast carcinoma cells in culture.

Four cell lines, each derived from a primary tumor from a patient with breast carcinoma, were grown to confluence in alpha-Minimum Essential Medium with 15% fetal calf serum and incubated for 24 h with [3H]androstenedione. The two lines (SA and PP) with the lowest formation of estrone and estradiol (less than 0.1% conversion) were the most active in the formation of the 5 alpha-reduced androgen metabolites androsterone (AND), 5 alpha-androstanedione (5 alpha-A-dione), and dihydrotestosterone (DHT). The two lines with the highest aromatase activity (DM and MD) had the lowest formation of 5 alpha-reduced metabolites. To determine if the 5 alpha-reduced androgen metabolites formed within the breast carcinoma cells could influence aromatase activity, the MD line was further studied. After 24-h preincubation with AND, DHT, or 5 alpha-A-dione at concentrations of 10(-6), 10(-7), and 10(-8) M, [3H]androstenedione was added to the culture medium, and aliquots were removed at 0, 4, 8, and 24 h. An 8-h incubation period was found to be optimum for inhibition studies. In comparison to control levels of estrone (2.5%) and estradiol (0.35%) formation, inhibition of aromatization was evident with all three compounds at 10(-8) M, with 5 alpha-A-dione producing the greatest inhibition (50%). At 10(-7) M, inhibition ranged from 45% (AND) to 70% (5 alpha-A-dione), and at 10(-6) M, inhibition was greater than 90% for each compound. 5 alpha-A-dione produced slightly greater inhibition than AND or DHT at each concentration tested. Since each of these compounds was capable of inhibiting aromatization, the cumulative effect of these 5 alpha-reduced metabolites could be an important factor in the intracellular regulation of aromatase activity.

Androstenedione↗

PubMed1984

Human minimal androgen insensitivity with normal dihydrotestosterone-binding capacity in cultured genital skin fibroblasts: evidence for an androgen-selective qualitative abnormality of the receptor.

We have studied a kindred in which two parts of siblings, maternal first cousins, have a form of "minimal" androgen insensitivity that permits morphogenesis of unambiguous male external genitalia, but interferes with normal virilization at puberty. All four had gynecomastia that required reductive surgery. Apart from this common phenotype, they varied considerably in the temporal and regional aspects of their subvirilization and appreciably in their androgenic responsiveness to pharmacological doses of testosterone. The cultured genital skin fibroblasts from one set of siblings have an androgen-receptor activity with the following properties: (1) a normal maximum-binding capacity (Bmax) with 5 alpha-dihydrotestosterone (DHT), or the synthetic androgen, methyltrienolone (MT; R1881) as ligand; (2) a higher than normal apparent equilibrium dissociation constant (Kd) for DHT (0.77 nM) but not for MT; and (3) an elevated dissociation rate (k) of DHT-receptor (0.013 min-1, 37 degrees C), but not MT-receptor, complexes within intact cells. In addition, prolonged incubation with MT, but not DHT, augments the specific androgen-binding activity of the mutant cells as much as that of the controls. Normal cells yield lower values of apparent Kd for DHT (0.1-0.3 nM) after 2- than after 0.5-hr incubation (0.3-1.8 nM), and 1-hr values are intermediate. This occurs despite concurrent catabolic consumption of DHT from the medium and is considered to reflect transformation of initial, low-affinity DHT-receptor complexes to subsequent, higher-affinity states by a process that depends on time and initial ligand concentration. The mutant complexes described here can readily attain the highest state of affinity with MT, but have an impeded, variably expressed ability to do so with DHT. These findings suggest that a structural mutation at the X-linked locus that encodes the androgen-receptor protein is responsible for its androgen-selective dysfunction. Synthetic, nonhepatotoxic androgens, with corrective effects in vitro comparable to those of MT, may be therapeutically useful for these subjects.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

PubMed1983

Mammosomatotroph cell adenoma of the human pituitary: a morphologic entity.

Nine cases of a hitherto undescribed morphologic entity, termed mammosomatotroph cell adenoma of the human pituitary, are reported. These tumors, occurring mostly in men, are invariably associated with acromegaly (or gigantism) and high-normal or slightly elevated blood prolactin levels, and it cannot be distinguished clinically from well-differentiated growth hormone cell or mixed growth hormone cell-prolactin cell adenomas. They show a slow growth rate and usually exhibit a diffuse pattern and intense cytoplasmic acidophilia by histology. The immunoperoxidase technique detects both growth hormone and prolactin within the same cells. Electron microscopy reveals monomorphous tumors with a fine structure markedly similar to that of well-differentiated, densely granulated growth hormone cell adenomas. An added feature and diagnostic marker of mammosomatotroph cell adenoma is the presence of extracellular deposits of secretory material. One tumor shows a marked abnormality of hormone packaging and storage, resulting in the cytoplasmic accumulation of pleomorphic bodies containing semicrystalline secretory material.

Acromegaly↗

PubMed1983

The metabolism of androstenedione and testosterone to C19 metabolites in normal breast, breast carcinoma and benign prostatic hypertrophy tissue.

In previous studies from our laboratory of the metabolism of androstenedione (A) and testosterone (T) in breast adipose and breast carcinoma tissue, the aromatization of these compounds, and their interconversion were demonstrated. The present study describes the conversion of androstenedione and testosterone to C19 metabolites in homogenates of normal breast tissue and breast carcinoma tissue and examines the C19 metabolites in homogenates of benign prostatic hypertrophy (BPH) tissue under similar conditions. Tissue homogenates were incubated for 90 min in Krebs-Ringer bicarbonate buffer (pH 7.4) with ATP (3 mM) and NADPH (2.4 mM) as co-factors. Following extraction with ethyl acetate, the metabolites were separated into neutral and phenolic fractions. Identification of specific products was made by thin layer and paper chromatography and recrystallization procedures. The formation of C19 metabolites was 10-fold greater in prostate than in breast tissue. Androsterone was the major product of androstenedione in both breast and prostate. The other 5 alpha-metabolites of androstenedione identified were dihydrotestosterone (DHT) and epiandrosterone (EPI). The 5 beta-metabolite, etiocholanolone (ET10), was identified in both breast and prostate following incubation with androstenedione. Using testosterone as substrate, dihydrotestosterone was the major product in normal breast and BPH. Etiocholanolone was detected in breast, but not in prostate following incubation with testosterone. Aromatization was demonstrated in all incubations with breast tissue, but not in prostate. The results indicate that androstenedione is actively metabolized by both breast and prostate to 5 alpha reduced metabolites. They also identify the formation of etiocholanolone in both tissues. Aromatization was demonstrated only in breast tissue.

Androstenedione↗

PubMed1983

Androstenedione metabolism in epithelial cells derived from early-lactation human milk.

Epithelial cells derived from duct epithelium were cultured from early lactation human milk in medium supplemented with 15% fetal calf serum, insulin (0.3 u/ml), cortisol 21-sodium succinate (6 micrograms/ml) and amikacin (50 micrograms/ml). The capacity of these cells to metabolize androstenedione to estrone, estradiol and C19 metabolites was studied during continuous culture. After extraction of the medium, the products were subjected to phenolic partition and separated by thin-layer and paper chromatography, followed by recrystallization to constant specific activity. The study demonstrated a progressive increase in the formation of estrone and testosterone over the first 24 h in culture, while estradiol formation showed an initial 2-4 h lag, then increased slowly. The C19 compounds identified were androsterone, 5 alpha-androstanedione, epiandrosterone, dihydrotestosterone and etiocholanolone. 5 alpha-Androstanedione and androsterone were the major 5 alpha-reduced metabolites. Since these cells are derived from normal duct epithelium, their metabolic characteristics may be more representative of normal breast tissue than those of tissue removed from patients with pathological breast disorders.

Androgens↗

PubMed1983

Systemic lupus erythematosus in males.

A study of 51 males being followed in the Wellesley Hospital Toronto SLE Clinic examined the questions of whether SLE in males was similar to that in females and whether affected males differ from unaffected males with respect to their maleness and sex hormone profile. Fifty of the men were phenotypically males, and one was known to have Klinefelter syndrome (karyotype 47 XXY). All had four or more 1982 revised criteria for SLE. Fifty females matched with respect to age and duration of disease were used as controls. In examining the spectrum of the disease, 21 clinical and laboratory manifestations were assessed. Although neurologic involvement, alopecia, and thrombocytopenia were less common and pleuritis more common in the males, none of these was statistically significant. Comparison of disease severity revealed only one statistically significant difference: the mean duration of corticosteroid usage was longer in the females. There was also a tendency for cytotoxic agents to be used more frequently in the females. It was thus concluded that spectrum and severity of the disease tended to be similar in males and females. The frequency of positive family histories for SLE and other autoimmune diseases was similar in males and females. The age of onset tended to be more evenly distributed in males than in females, with one quarter of the males diagnosed after the age of 50. HLA typing revealed increased frequencies of the B8 and DR3 antigens in the SLE males compared with normal controls, as had previously also been shown for SLE populations with a female preponderance.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1982

Aromatase in human breast carcinoma.

Breast carcinoma tissue is capable of forming estrogens from circulating androgen precursors. In this study, aromatase was examined in homogenates of breast adipose and breast carcinoma tissue, in normal and abnormal parenchymal breast tissue, and in breast carcinoma cells in culture. Homogenates of carcinoma tissue showed a wide range of activity in the conversion of adrostenedione to estrone. The mean conversion in carcinoma tissue was greater than that seen in parenchymal tissue from patients with gynecomastia and mammary dysplasia. Homogenates of breast adipose tissue from patients with benign and malignant disorders showed comparable aromatase activity. Three cell lines isolated from a primary breast carcinoma differed in their aromatase activity demonstrating a heterogeneity of aromatase activity in cells from a single tumor. Studies of aromatase activity in breast carcinoma cells in culture over a period of 8 hr demonstrated progressive estrone formation. Testosterone formation from androstenedione was noted in all studies using both homogenates and cell cultures. Testosterone formation from androstenedione was approximately 10-fold greater than was the formation of estrone from androstenedione in all studies. The metabolism of androstenedione to other androgens examined in homogenates of normal and carcinomatous breast tissue revealed that the major products were androsterone, 5 beta-androsterone, dihydrotestosterone, and epiandrosterone. Both estrogen and androgen formation within the cell may be important in determining the cellular response.

Adipose Tissue↗