TGF-beta superfamily members including bone morphogenetic proteins (BMPs) and their receptors (BMPR-1A, -1B and -2) have been shown to be important for reproductive function in both males and females, while information on the role of BMPs in males is limited. Functional studies on select BMPs and BMP receptors have demonstrated vital roles for these proteins in somatic and germ cell proliferation, steroidogenesis and overall fertility. In order to gain insight into the importance of these genes during postnatal reproductive development in males, our study was undertaken to specify the distribution of BMP and BMPR mRNA in male reproductive and steroidogenic tissues and quantify these genes in the testis using the mouse as our model. We screened testis at two, four, six and eight weeks of age for the expression of ten BMPs and three BMP receptors using RT-qPCR. All three BMP receptor mRNAs - Bmpr1a, Bmpr1b and Bmpr2, and ten BMP mRNAs - Bmp2, Bmp3, Bmp3b, Bmp4, Bmp5, Bmp6, Bmp7, Bmp8a, Bmp8b and Bmp15 were expressed in mouse testis at all stages screened. Testicular expression of genes varied within age groups and at specific developmental stages. Our study establishes an extensive BMP system in mouse reproductive and steroidogenic tissues.
- MeSH
- Bone Morphogenetic Proteins metabolism MeSH
- Mice MeSH
- Bone Morphogenetic Protein Receptors metabolism MeSH
- Seminal Vesicles growth & development MeSH
- Aging metabolism MeSH
- Testis growth & development metabolism MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Comparative Study MeSH
This study tested and compared the anti-proliferative and proliferative activities of two anti-oestrogens and three anti-progestins on four separate mouse model systems: young intact and adult ovariectomized (OV-X) females, and young intact and adult castrated males. Pure steroidal anti-oestrogen ICI 182,780 (ICI) decreased mammary and uterine growth stimulated by endogenous hormones in young intact females and by exogenous hormones [progesterone (Prog), 17beta-oestradiol (E) or E plus Prog] in both young intact and adult ovariectomized (OV-X) females. Non-steroidal anti-oestrogen EM-800 (EM), on the other hand, had no effect on mammary and uterine growth stimulated by endogenous hormones in young intact females and in adult OV-X females. Uterine growth was even stimulated by EM alone, and a combination of EM plus Prog not only stimulated uterine growth but also mammary growth (an oestrogenic agonistic activity). However, EM showed anti-oestrogenic activities in both mammary and uterine tissues in females treated with E or E plus Prog. In males, ICI and EM decreased mammary growth stimulated by exogenous hormones (E or E plus Prog) in both young intact and adult castrated animals. In young intact, but not in adult castrated males, ICI increased seminal vesicle growth affected by both endogenous and exogenous (Prog, E or E plus Prog) hormones. EM, on the other hand, decreased seminal vesicle weights in E or E plus Prog and increased its weights in Prog-treated young intact males. Thus, under certain conditions EM possess mixed agonist and antagonist activity in the mammary gland, uterus and seminal vesicles. Norethindrone acetate (NA)-stimulated mammary growth was decreased by anti-progestins onapristone (ON), RU 46556 (RU), and RU 38486 (MI) by 34-59% in females and by 35-93% in males. Uterine weights of NA-treated females were decreased by ON and RU by 29-55% but not by MI. In NA-treated young intact males, seminal vesicle weights were stimulated by RU (by 63%) and not affected by ON and MI. In NA-treated adult castrated males, seminal vesicle weights were decreased by ON, increased by RU and not affected by MI. The results obtained in these and our earlier studies show clearly that mouse four-model systems could serve as in vivo tool for the detection of steroid hormone agonist and antagonist activities of natural and man-made chemicals.
- MeSH
- Estrogen Antagonists pharmacology MeSH
- Biological Assay MeSH
- Financing, Organized MeSH
- Castration MeSH
- Mammary Glands, Animal growth & development drug effects MeSH
- Models, Animal MeSH
- Mice, Inbred C3H MeSH
- Mice MeSH
- Progesterone antagonists & inhibitors MeSH
- Seminal Vesicles growth & development drug effects MeSH
- Uterus growth & development drug effects MeSH
- Organ Size drug effects MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Mice MeSH
- Female MeSH
- Animals MeSH
- MeSH
- Estradiol administration & dosage physiology MeSH
- Research Support as Topic MeSH
- Castration utilization MeSH
- Mammary Glands, Animal physiology growth & development drug effects MeSH
- Mice MeSH
- Progesterone administration & dosage physiology MeSH
- Seminal Vesicles physiology growth & development drug effects MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Mice MeSH
- Animals MeSH
