The three dominant oxidative biotransformations of estradiol were examined in 10 normal women and 33 females with breast cancer by using a recently devised radiometric method. Estradiol tracers, labeled with 3H specifically in the 17a, C-2, or 16a position, were used to measure both the rate and extent of 17P-ol oxidation (the initial metabolic step) and the subsequent 2-and 16a-oxidative reactions. The mean ± SEM values for the extent of estradiol metabolism at these three specific sites were 76.9 ± 5.3%, 31.1 ± 4.0%, and 9.3 ± 0.8%, respectively, in normal subjects. Corresponding data in patients with breast cancer-i.e., 73.0 ± 4.2%, 32.7 ± 2.7%, and 14.9 ± 1.5%-revealed a significantly greater extent of 16a-hydroxylation in the latter population. Because the 16a-hydroxylated compounds (including estriol) are themselves potent estrogens, these changes may have important hyperestrogenic consequences that could have a bearing on the etiology of the disease.Endocrine factors have been implicated in the initiation or promotion, or both, of mammary tumorigenesis based on data collected from several sources. These include both experimental studies using animal models and epidemiological and clinical investigations in human subjects (1). Thus, certain features of the menstrual history and age at parity, which can lengthen the period ofexposure to estrogens secreted by the ovaries, appear to be associated with an increased risk for the disease (2, 3). On the other hand, oophorectomy prior to age 35 can lessen the risk of breast cancer (3). Because an augmentation in estrogen secretion could be implicated in the etiology of the human disease, numerous studies have been conducted to detect such an increase in women with, or at high risk to develop, breast cancer (4). Although some investigators have reported significant differences in urinary or plasma estrogen levels, or both, between these subjects and normal individuals (5-7), these findings have not been consistent and have been challenged by others (8, 9). An alternative and possibly more viable hypothesis that an alteration in estrogen metabolism is associated with breast cancer (4, 10) has also been the subject of extensive investigations.The metabolism of estradiol, which is primarily oxidative, consists ofan initial oxidation ofthe 17/3-hydroxy group to yield estrone. This steroid is subsequently metabolized mainly through either of two alternate hydroxylative pathways; namely, hydroxylation at the C-2 or the 16a position (11). These hydroxylations are of particular interest in that they constitute competing reactions whose products are themselves active compounds characterized by markedly different biological properties. The 16a-hydroxyestrogens-estriol and 16a-hydroxyestrone-demonstrate uterotropic activity comparable to that of the parent hormone, estradiol (12, 13). On the other hand, the principal 2-hydroxyestrogens-2-hydroxyestrone and 2-methoxyestrone exhibit virtually no peripheral estrogenic effects but appear to play a regulatory role in neur...

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Injection of 70/30 insulin before supper safely restored glycemic control of type 2 diabetes not controlled by glimepiride alone. Control was restored more rapidly and with less injected insulin when glimepiride was continued.

Two three-year-old boys with dwarfism (height ages 1-4/2 and 1-11/12 years) and delayed bone ages (1-4/12 and 1-9/12 years) had normal growth hormone (GH) responses after stimulation and low levels of somatomedin. Unlike patients with Laron syndrome, the two patients generated normal levels of somatomedin after administration of exogenous hGH. Treatment with hGH (2 IU every other day) brought about a significant increase in the growth rate of both patients. The growth rate of the first patient increased from 2 cm/year before treatment to 12 cm/year on therapy. The growth rate of the second patient was 4.5 cm/year before treatment, and 8.3 cm/year while on treatment. The two cases represent a new syndrome of dwarfism which may be caused by secretion of a biologically inactive but immunoreactive GH.