Induction of Hypothyroidism and Hypoprolactinemia by Growth Hormone Producing Rat Pituitary Tumors

Abstract

The GH3 rat pituitary tumor cell line which secretes growth hormone (GH) and prolactin (PRL) stopped releasing PRL when transplanted to animals. It suppressed PRL production by the hosts'' pituitary glands. When the same tumor was transferred back to cell culture, PRL production resumed. The PRL:GH ratio in cell culture medium and cells ranged from 5-1, while in the tumor and in serum of the host animals it averaged 0.09 and 0.001, respectively. To investigate further this phenomenon, female rats were transplanted with GH3 tumors (T) and compared to intact normal (N) and thyroidectomized (Tx) rats. T animals were larger and had splanchnomegaly but smaller pituitaries and thyroids. Serum PRL concentrations in the basal state were decreased, as were levels of triiodothyronine (T3), thyroxine (T4) and free T4 index. Despite reduced serum thyroid hormone concentration, and in contrast to Tx animals, the serum thyrotropin (TSH) level in T rats was not elevated and they did not show a supranormal TSH response to thyrotropin-releasing hormone (TRH) administration. The PRL response to TRH in T animals was completely abolished while all N and Tx animals responded by a significant increase in serum PRL. Serum corticosteroids and estrogens were normal in T rats. Pituitary content of PRL was decreased and that of TSH increased in T rats. Tx animals had a reduced pituitary content of PRL, TSH and GH. When GH3 cells were grown in cell culture media containing serum from T animals, there was a reduction of PRL content in cells and released in the medium. Addition of T3 to the T serum did not alter its suppressive effect on PRL nor did rat GH added to N serum alter PRL production and release in vitro. In a preliminary experiment, rats injected i.p. with 50 .mu.g hGH in 2 divided doses for 8 days, suppressed serum T4 and T3 concentrations. Pituitary content of TSH was significantly increased and that of PRL was slightly decreased. Injection with 250 .mu.g of PRL or saline, on the same schedule and for the same length of time, had no significant effect on the levels of serum thyroid hormones. GH, but also possibly other substance(s) secreted by GH3 tumors in vivo suppress the production of tumor and pituitary PRL; suppress the release of TSH, causing mild hypothyroidism: inhibit the PRL and TSH responses to TRH and decrease the production of PRL in tissue culture. Although no simple and unifying theory could explain these findings, a hypothesis implicating somatomedin is presented.