Jan C. Birkenhäger

The effect of growth hormone administration in growth hormone deficient adults on bone, protein, carbohydrate and lipid homeostasis, as well as on body composition

OBJECTIVE The effect on bone, protein, carbohydrate and lipid homeostasis as well as body composition of the administration of growth hormone to adult patients with growth hormone deficiency was studied.

Consequences of vitamin D receptor gene polymorphisms for growth inhibition of cultured human peripheral blood mononuclear cells by 1, 25-dihydroxyvitamin D3.

In the vitamin D receptor (VDR) gene a BsmI restriction fragment length polymorphism (RFLP) in intron 8 and a translational start‐site polymorphism, identified as a FokI RFLP, have been described. Crucial for a proper interpretation of these polymorphisms in association studies is the knowledge whether they have direct consequences for 1,25‐(OH)2D3 action at cellular level. The present study was designed to assess functional significance of the FokI and BsmI VDR gene polymorphisms in peripheral blood mononuclear cells (PBMC) with a natural occurring VDR genotype for cell growth inhibition by 1,25‐(OH)2D3.

SEX HORMONE BINDING GLOBULIN IN POSTMENOPAUSAL WOMEN: A PREDICTOR OF OSTEOPOROSIS SUPERIOR TO ENDOGENOUS OESTROGENS

To quantify the role of endogenous oestrogen activity in osteoporosis we measured relative metacarpal cortical area (RCA), body mass, serum oestrone, oestradiol, androstenedione, and sex hormone binding globulin (SHBG) in 746 postmenopausal women aged 53 to 76 years, sampled from the general population. The occurrence of fractures and the rate of loss of RCA (delta‐RCA) were determined over the previous 9 years. Both RCA and delta‐RCA were significantly related to body mass, serum oestrone, oestradiol, and SHBG. The influence of the first three variables appeared to be bone preserving, whereas the latter appeared to be bone wasting. Serum oestradiol, SHBG and body mass proved to have an independent relationship with RCA in multivariate regression analysis. The relationship to delta‐RCA was statistically independent for serum SHBG only. Serum androstenedione was unrelated to either RCA or delta‐RCA. In the total study population, body mass, serum oestrone, oestradiol and SHBG were not related to the occurrence of fractures over the previous 9 years. In the subgroup of 249 elderly women, aged 65‐76 years, SHBG levels were significantly higher for women with type I osteoporotic fractures (vertebral and forearm fractures) as compared to controls. The results suggest a bone wasting influence of SHBG in postmenopausal women, possibly resulting in an increased risk of type I osteoporotic fractures in elderly women.

The Value of the Thyrotropin-Releasing Hormone Test in Patients with Prolactin-Secreting Pituitary Tumors and Suprasellar Non-Pituitary Tumors

The prolactin (PRL) response to thyrotropin-releasing hormone (TRH) (delta PRL) was normal in 7 (18%) of 38 patients with clinical evidence of a prolactinoma. A negative percentage correlation between basal PRL and delta PRL was found (P less than 0.05), but a percentage correlation between tumor size and delta PRL was absent. In a survey of literature concerning 548 patients, delta PRL after TRH administration amounted to 100% or more of the basal value in 11% of patients with clinical evidence of a prolactinoma and in 9% with an adenoma proven by surgery. Hyperprolactinemia was also present in 12 of our 21 patients (57%) with suprasellar tumors not related to pituitary tumors. In 7 of 11 of these hyperprolactinemic patients (64%), the PRL response to TRH was decreased. In conclusion, the TRH test may be helpful but is not decisive in the diagnostic work-up of hyperprolactinemia patients.

Growth Hormone Normalizes Low-Density Lipoprotein Receptor Gene Expression in Hypothyroid Rats

Hypothyroidism leads to a decreased activity of the low-density lipoprotein (LDL) receptor, which contributes to the hypercholesterolemia frequently seen during hypothyroidism. It is not known whether the decreased activity of the LDL receptor is directly due to the absence of thyroid hormone, or secondary to a deficiency of growth hormone (GH). Therefore, the effect of GH administration on LDL receptor activity was studied in hypothyroid rats. Following induction of hypothyroidism, the level of LDL receptor mRNA was significantly decreased in liver homogenates to 31 % +/- 6% of the control value. LDL binding to liver cell membranes and plasma membranes decreased during hypothyroidism to approximately 65% of the control value. The effect of hypothyroidism on the hepatic LDL receptor was reflected in a significantly increased half-life of (125)I-LDL of 29 hours in controls versus 48 hours in hypothyroid rats. Treatment of hypothyroid rats with human GH (hGH) resulted in normalization of both the amount of hepatic LDL receptor mRNA and LDL binding on liver cell membranes. The plasma half-life of human (125)I-labeled LDL decreased during GH substitution but did not normalize. GH treatment significantly reduced plasma LDL cholesterol levels by 36% (P < .05, n = 8), to levels that were still higher than in control animals. These data indicate that at least part of the decreased LDL receptor activity during hypothyroidism is secondary to GH deficiency.

Value of Luteinizing Hormone-Releasing Hormone Testing in Bromocriptine Treatment of Amenorrhea and Hyperprolactinemia in Patients with Pituitary Tumors

The results of bromocriptine treatment in 13 patients with radiologically evident pituitary tumors are described. A menorrhea was present in all patients, hyperprolactinemia in 12 of the 13 patients, and acromegaly in 3 patients. Five patients have previously been treated surgically and by radiotherapy because of suprasellar extension of the adenoma. Plasma prolactin levels after one single dose of 2.5 mg of bromocriptine were found to have no predictive value as to the dosage needed for treatment, whereas the plasma gonadotropin response after the administration of luteinizing hormone-releasing hormone appeared to be predictive with respect to the return of ovulation during bromocriptine therapy.