EXPRESSION OF INHIBIN ACTIVIN SUBUNIT MESSENGER RIBONUCLEIC-ACIDS DURING RAT EMBRYOGENESIS

Inhibin (alpha/beta) and activin (beta/beta) were first recognized as gonadal hormones that regulate the production and release of FSH from the anterior pituitary gland. Studies now show that these proteins, which are members of the transforming growth factor-beta (TGFbeta) superfamily, and their corresponding messenger RNAs have a broad anatomical distribution and may regulate the growth and differentiation of a variety of cell types. To determine whether inhibin and activin may also play a role in embryonic development, in situ hybridization techniques were utilized to examine the localization of the mRNAs encoding the inhibin/activin subunits (alpha, beta-A, beta-B) in rat embroys from 12 days post coitum (p.c.) until birth. The beta-A-subunit message was localized in the heart at 12 days p.c. and in the dermal layer of the skin starting at 13 days p.c. At 14 days p.c. this mRNA was first observed in the whisker follicles, in the developing skeleton of the snout, limbs, and in the intervertebral disks. At 16 days p.c. the beta-A-message was found in the striatum of the brain, and at 18 days p.c. it was also detected in the cerebral cortex. The beta-A-mRNA signal appeared in hair bulbs at 17 days p.c., in teeth at 18 days p.c., and in tendons and gonads just before birth. Expression of beta-A-mRNA was no longer detected in the skin or intervertebral disks after 17 days p.c. The beta-B-subunit message was found in the area of rapidly dividing cells surrounding the forebrain ventricle, starting at 14 days p.c., in the gonads from the time of gonadal sexual differentiation, at 14 days p.c., and in the salivary gland as early as 17 days p.c. The beta-B-message continued to be expressed in these areas throughout embryogenesis. The inhibin-alpha subunit message was also detectable in the gonads from 14 days p.c. until birth. These data suggest that 1) inhibin and activin may be produced in the gonads and possibly play a hormonal role in the embryonic rat during the last trimester of pregnancy, and 2) activin may regulate aspects of the embryonic development of the heart, skin, hair and whiskers, cartilage, bone, tendons, teeth, salivary gland, brain, and gonads, possibly in coordination with other members of the TGF-beta superfamily whose mRNAs are expressed in some of these same tissues during development.