Hypophysectomy Inhibits Wound Hyperplasia in the Adult Frog Lens

Abstract

The experiments reported herein prove that wound-associated hyperplasia of frog lenses is inhibited after hypophysectomy. Proliferation can be restored by replacement therapy with either frog pituitary powder or bovine somatotropin. When this is done, division figures are observed after 6 days in the environs of the wound focus and 2 days later in the germinative zone. In the absence of an injury, heightened mitotic activity typically occurs in the germinative zone and subsequently in the polar region. Wound cells in both intact and hypophysectomized frogs bind more tritiated actinomycin D than do cells in the lenses from uninjured frogs. In the latter, the amount of ³H-actinomycin bound does not seem to be affected by hypophysectomy. Wound closure occurs in experimental as well as control animals but the patterns of closure are different. We suggest that cells near the injury in the lenses of hypophysectomized animals may move from G₀ to G₁ but are stalled in the latter stage of the cycle.

G0/G1Arrest of Cell Proliferation in the Ocular Lens Prevents Development of Radiation Cataract

“…As noted earlier [Van Buskirket al, 1975;Rothstein et al, 1976], mitotic activity in the germinative zone of the frog lens disappears 3-4 weeks posthypophysectomy; we have never observed any such effect in rodent lenses. One author claims a modest change in prolif eration kinetics in the lens epithelium of hypophysectomized rats [Cotlier, 1962], The Rana pipiens blockade of cell division leads to a failure of migration of epithelial cells into the lens bow.…”

“…The hypothesis mentioned can be conveniently tested now, because hypophysectomy causes all lens mitosis to subside in frogs [ Van Buskirk et al, 1975Rothstein et al, 1976, whereas in rats this effect, if it occurs at all, is minor [Cotlier, 1962], The hypophysectomy-associated arrest of cell proliferation in frogs may be traced to a requirement for insulin-like growth factors probably generated in the liver under the influence of growth hormone, prolactin, triiodothyronine and thyroxin Wainwright et al, 1976;Weinsieder and Roberts, 1980;Wein-sieder and Rothstein, 1980]. Hence, the state of mitotic arrest caused by pituitary ablation is reversed by injection of purified human somatomedin C [Rothstein et al, 1980b) multiplication stimulating activity (MSA) or insulin [Rothstein et al, 1980a], These materials also restore proliferation in organ-cultured lenses from hypophysectomized frogs, whereas the pre viously noted pituitary and thyroidal hormones are only active in vivo [Wainwright et al, 1978].…”

Ultrastructural immunocytochemical localization of fibronectin deposition during corneal endothelial wound repair. Evidence for cytoskeletal involvement

“…Thus migration, in the absence of mitosis, plays the major role in endothelial wound response. A similar situation has been described for injured lens epithelium of hypophysectomized animals [45], where cells migrate into the region of a mechanical wound in the absence of mitosis. In other systems, such as skin [34] and corneal epithelium [36], migration is a major mechanism of repair.…”

Ultrastructural Changes Associated with the Induction and Reversal of a Chemically Induced Cataract

“…Relative to the lens in situ, W o r g u l , and M erriam [1977] reported that endotoxin-induced uveitis in rats is associated with in creased lenticular mitotic activity. On the other hand, Rothstein et al [1976] have shown that the normal mitotic activity of the amphibian lens is dependent on the presence of an intact pituitary gland. Thus, proliferative activity in the injured and uninjured lens may, to some extent, be under extraocular control.…”