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To determine if the mode of 17 beta-estradiol (E2) administration affects growth hormone (GH) concentrations, eight postmenopausal women were studied under the following conditions: (1) control (no E2), (2) oral E2 (Estrace, 1 mg every 12 h for 2 weeks) and (3) transdermal E2 (Estraderm patch, 0.1 mg, two patches changed daily for 2 weeks). Blood was collected every 5 min for 24 h and assayed for serum GH concentrations using a sensitive chemiluminescence assay. Serum E2 levels were comparable during both E2 treatment regimens when measured with a specific chemiluminescence assay. The 24-h integrated GH concentrations (IGHC, min . micrograms/L) increased in all eight subjects from (mean +/- SE) 494 +/- 102 during control to 860 +/- 111 (P0.05) and 832 +/- 149 (P0.05) during oral and transdermal E2, respectively. Both E2 treatments significantly increased GH pulse height, individual pulse area, incremental pulse amplitude, interpeak valley concentration, and interpeak valley nadir (as measured by Cluster algorithm) when compared with control. No significant differences were observed in the number of GH pulses per 24 h. Insulin-like growth factor-I (IGF-I, micrograms/L) concentrations decreased from 165 +/- 19 (control) to 109 +/- 11 (oral E2, P0.05) and 122 +/- 15 (transdermal E2, P0.05). No statistically significant differences in attributes of pulsatile GH release or IGF-I concentrations were observed between the oral and transdermal E2 treatments. We conclude that both oral and transdermal E2 treatment increase serum GH concentrations in postmenopausal women. This increase is manifested by larger GH pulses and higher basal (interpulse) GH levels, not by changes in pulse frequency. Both routes of E2 administration decrease serum IGF-I concentrations, which may attenuate IGF-I negative feedback on pituitary somatotrophs and hypothalamic somatostatin secretion, resulting in enhanced pulsatile GH release.

Gli attuali approcci terapeutici nella cura dell’acromegalia comprendono: la chirurgia, la radioterapia e la terapia farmacologica. Il pegvisomant e un nuovo antagonista recettoriale del GH che migliora la sintomatologia e i livelli sierici di IGF-1 in un’alta percentuale di pazienti trattati per 12 settimane. In tale studio si e valutata l’efficacia del farmaco in 160 pazienti con acromegalia trattati per circa 18 mesi. I soggetti hanno ricevuto il pegvisomant tramite iniezione sottocutanea giornaliera con una dose iniziale di 10 mg/die e con dose massima raggiungibile di 40 mg/die. La dose di farmaco da somministrare e stata valutata mediante dosaggio bisettimanale o mensile dell’IGF-1.Trenta dei 160 pazienti arruolati hanno abbandonato prematuramente il protocollo di studio. Dopo 12 mesi di trattamento il 97% dei pazienti mostrava normali livelli di IGF-1. Effetti collaterali si sono verificati nel 10% dei soggetti, generalmente di lieve entita. Solo in 2 pazienti si e avuto un incremento delle transaminasi rientrate nella norma alla sospensione del farmaco. In altri 2 pazienti si e evidenziato un incremento volumetrico della massa tumorale. Il pegvisomant sembra essere, quindi, un ulteriore efficace arma nella cura della patologia acromegalica, soprattutto per i soggetti resistenti o scarsamente responsivi alla terapia con analogni della somatostatina.

Thirty-four human pituitary adenomas were examined for the presence of Pit-1 mRNA via Northern analysis. All tumors that were immunoreactive with either human (h) PRL or hGH antiserum contained Pit-1 mRNA (8 of 8) as did a small percentage of alpha-subunit only (1 of 3) and null tumors (1 of 9). Two tumors that contained TSH beta mRNA by RNAse protection assay also contained Pit-1 mRNA. Tumors that were immunoreactive with antiserum for hACTH, hFSH beta, or hLH beta without containing PRL, GH, or TSH beta were uniformly Pit-1 negative (0 of 14). Although RNA from the majority of Pit-1-positive tumors (10 of 11) contained primarily a 2.4-kilobase (kb) Pit-1 mRNA transcript, 1 tumor appeared to contain a 1.6-kb mRNA. Analysis of human pituitary autopsy specimens revealed no 1.6-kb Pit-1 mRNA, indicating that this variant may be tumor specific. The wide variety of serum PRL, GH, and insulin-like growth factor-I levels in patients with Pit-1-positive tumors suggests that although Pit-1 is necessary for PRL and GH production, it is not uniformly associated with hormone production, as determined by either immunohistochemistry or elevated serum levels. The expression of Pit-1 mRNA in a small fraction of null and alpha-subunit only tumors indicates that there may be a previously unsuspected diversity of origin within these particular subsets of adenomas.

Increasing evidence has accumulated in support of the hypothesis that growth hormone (GH) and insulin-like growth factors (IGFs) play a role in carcinogenesis. In order to test this hypothesis, female nude mice were xenografted with two different human colorectal cancer cell lines (COLO 205 and HT-29) and randomized to receive placebo or a GH receptor antagonist (GHRA) (B2036-PEG) every second day for 16 days. The tumour volume was measured in each animal throughout the study and by the end of the experiment the tumour weights were recorded. After 16 days of therapy in nude mice with the COLO 205 colorectal cancer, GHRA treatment caused a 39% reduction in tumour volume (p0.02) and a 44% reduction in tumour weight (p0.01). GHRA treatment equally reduced circulating IGF-I and IGFBP-3 levels, while apoptosis was increased in the treatment group. Expression of IGF-I, IGF-II and the corresponding receptors in COLO 205 tumours was also decreased by the treatment. GHRA had no effect on the growth of the HT-29 colorectal cancer despite pronounced reduction in serum IGF-I. The present study thereby demonstrates a central role for the GH/IGF system in the pathogenesis of some colorectal cancers and suggests that specific GHR blockade may present a new concept in the treatment of colorectal cancer.

Forty-one human pituitary adenoma specimens were examined for the presence of estrogen receptor (ER) messenger ribonucleic acid and protein using a combination of ribonuclease protection assay, [3H] estradiol ([3H]E2) binding, and ER immunohistochemistry. ER messenger ribonucleic acid prevalence was high in PRL-immunoreactive tumors (2 of 2), moderate in GH/PRL tumors (2 of 5), and low or absent (0 of 4) in GH tumors. In the GH/PRL-immunostaining tumors, the presence of the ER was uniformly associated with elevated serum PRL levels. Among the gonadotropin-immunostaining tumors, 10 of 17 were ER positive; within this group, those with gonadotroph adenoma characteristics were ER positive, whereas those with null cell/oncocytic characteristics were ER negative. Of the tumors that did not immunostain for any known anterior pituitary hormones, 3 of 11 were ER positive. ER immunohistochemistry in 14 tumors revealed a 100% correlation with ribonuclease protection assay results, whereas [3H]E2 binding, determined in 9 tumors, showed an 87% correlation. In summary, it appears that PRL and a specific class of gonadotropin-immunostaining tumors (identifiable by specific characteristics on electron microscope) contain ER, whereas GH-immunostaining tumors are ER negative. ER expression in normal pituitary paralleled that in macroadenomas (GH, 2.3%; PRL, 50%; FSH, 70%; LH, 83%; TSH, 4%; ACTH, 1%). The ER-positive tumors represent a subset whose growth and secretory profiles may be influenced by the gonadal steroidal milieu or by pharmacological agents that affect E2 levels or ER function.

Entering freshmen, second-semester freshmen, and sophomores through seniors were surveyed regarding their recent alcohol and drug use. Among entering freshmen, 81% drank and 34% used drugs. Compared to groups that had been at college longer, entering freshmen were a significant 16% lower for alcohol and 12% lower for drugs than the other groups, but all other groups showed no significant differences regardless of year in school. When analyzed separately by sex, all results were identical to this overall pattern except that drug use among women did not appear to increase substantially from entering students to later years. These results indicate a relatively rapid influence of the college environment which then leads to stability of substance use behavior.