Histomorphological perspectives of preputial and clitoral glands of soft-furred field rat Millardia meltada

The present study was an attempt to understand the sexual dimor-phism of the integumentary scent glands of soft-furred field rat Millardia meltada from the perspectives of anatomy, morphology and histology with view to correlate with the sex-specific pheromones they produce. The scent gland of male is known as preputial gland, and female, the clitoral gland. The rats, that are agricultural pests were field caught, the glands of males and females of almost identical size were dissected out, and subjected to gravimetric, morphometric and histological analyses. Both glands are yellowish-brown, pear-shaped, and dorsoventrally compressed. The mean weight, length and width of preputial glands are significantly (p < 0.05) larger than that of the clitoral glands. The preputial gland is composed of sebaceous glandular lobules and apocrine glandular lobules whereas the clitoral gland is formed only of sebaceous glandular lobules. The sebaceous glandular lobules of both preputial and clitoral glands are filled with a wax-like material. Thus, the scent glands of the soft-furred male field rats exhibit sexual dimorphism in respect histoarchitecture of the glands and the nature of the secretory material. This sexual dimorphism of the scent glands may reflect control by male and female sex hormones impinging on specific roles as sex attractant pheromones.

Differential androgen and estrogen substrates specificity in the mouse and primates type 12 17β-hydroxysteroid dehydrogenase

Recently, we have shown that human and monkey type 12 17β-hydroxysteroid dehydrogenases (17β-HSD12) are estrogen-specific enzymes catalyzing the transformation of estrone (E1) into estradiol (E2). To further characterize this novel steroidogenic enzyme in an animal model, we have isolated a cDNA fragment encoding mouse 17β-HSD12 and characterized its enzymatic activity. Using human embryonic kidney cells (HEK)-293 cells stably expressing mouse 17β-HSD12, we found that in contrast with the human and monkey enzymes, which are specific for the transformation of E1 to E2, mouse 17β-HSD12 also catalyzes the transformation of 4-androstenedione into testosterone (T), dehydroepiandroster-one (DHEA) into 5-androstene-3β,17β-diol (5-diol), as well as androsterone into 5α-androstane-3α,17β-diol (3α-diol). Previously, we have shown that the specificity of human and monkey 17β-HSD12s for C18-steroid is due to the presence of a bulky phenylalanine (F) at position 234 creating steric hindrance, preventing the entrance of C19-steroids into the active site. To determine whether the smaller size of the corresponding leucine (L) in the mouse sequence is responsible for the entrance of androgenic substrates, we performed site-directed mutagenesis to substitute Leu 234 for Phe in the mouse enzyme. In agreement with our hypothesis, the mutated enzyme has a highly reduced ability to metabolize androgens. mRNA quantification in several mouse tissues using real-time PCR shows that mouse 17β-HSD12 mRNA is highly expressed in the female clitoral gland, male preputial gland, as well as in retroperitoneal fat and adrenal of both sexes. The differential androgenic/estrogenic substrate specificity of type 12 17β-HSD in the mouse and primates seems to agree with the observation that androgen and estrogen in the mouse are provided almost exclusively by gonads, while in primates an important part of these steroid hormones are produced locally from adrenal precursors.

Carcinogenicity of 3,3'-Dimethylbenzidine Dihydrochloride Given in Drinking Water to F344/N Rats

3,3'-Dimethylbenzidine dihydrochloride (DMB) was evaluated for toxicity and carcinogenicity because of the potential for human exposure during production and use of bis-azobiphenyl dyes and because benzidine, a structurally related chemical, is a known human carcinogen. Two studies (9 and 15 months) were conducted by administering 0, 30, 70, or 150 ppm DMB (approx. 99% pure) in drinking water to F344/N rats. In the 15-month studies, 60 rats of each gender were used in the control group, 45 in the low-dose, 75 in the mid-dose, and 60 in the high-dose group. After exposure for 9 months, chemical-related neoplastic lesions were observed in the skin, Zymbal's gland, preputial gland, clitoral gland, liver, oral cavity, large and small intestines, and lung. Although designed for 24 months these studies were terminated after 15 months because significant numbers of treated rats were dying with tumors or were killed in moribund condition. Chemical-related nonneoplastic lesions included cystic degeneration and foci of alteration in the liver; exacerbation of nephropathy; hyperplasia of Zymbal's gland, preputial and clitoral glands, and alveolar epithelium. After exposure for 15 months, significantly increased incidences of neoplasms were observed at many organ sites: skin, Zymbal's gland, preputial and clitoral gland, liver, oral cavity epithelium, small and large intestines, mammary gland, lung, and mesothelium of treated rats. It is concluded that DMB is clearly carcinogenic for male and female F344/N rats.