Advanced carcinoma of the prostate: treatment with a gonadotrophin releasing hormone agonist.

Ten patients with advanced progressive adenocarcinoma of the prostate were treated with a long acting analogue of gonadotrophin releasing hormone. Eight of these patients responded to treatment in terms of pain relief and clinical regression of tumour. Serum gonadotrophin and testosterone concentrations were significantly suppressed by the end of the second week of treatment, testosterone concentrations being comparable with those achieved by castration. The two patients who failed to respond had both relapsed previously when receiving conventional treatment, and neither showed any endocrine response to the analogue. Superagonists of gonadotrophin releasing hormone may be the treatment of choice in adenocarcinoma of the prostate, but further trials are required to establish long term safety and efficacy.     

Reproductive characteristics of lambs actively immunized early in life with inhibin-enriched preparations from follicular fluid of cows

Active immunization of Merino and crossbred ewe lambs early in life with a partly purified inhibin derived from bovine follicular fluid (bFF) advanced their puberty. This occurred whether the lambs were immunized from 3 weeks of age or from 9 weeks of age or just 3 times between 3 and 9 weeks. However, the effect was more obvious with multiple injections starting at 3 weeks of age. The ovulation rate of the immunized lambs was significantly higher than that of the control ewes. When lambs were subjected to multiple immunizations the increased ovulation rate persisted in Merinos for at least 1 year after immunization ceased. The lambs injected 3 times only (at 3, 6 and 9 weeks of age) did not show any increase in ovulation rate. Plasma concentrations of FSH and LH measured in blood samples taken 1 week after immunization were not significantly different between the treatment groups. Daily sperm output in the urine and testis diameter were measured in ram lambs from the same breeds and flocks as the ewe lambs. Immunization with the inhibin preparation from 3 weeks of age resulted in a significant increase in daily sperm output (4255 +/- 701 vs 2344 +/- 344 x 10(6), P less than 0.01) and testis diameter (5.21 +/- 0.3 vs 4.33 +/- 0.2 cm, P less than 0.05) in Merino rams examined in the non-breeding season when the rams were aged 23 months. Although the same trend was seen in the following year the differences were not significant. Immunization from 9 weeks of age had no effect. A similar increase in daily sperm output was seen (at 20 and 25 months of age) in crossbred rams immunized from 3 weeks of age but the difference was not significant. Plasma concentrations of FSH (but not LH) in samples from rams immunized from 3 weeks of age were significantly higher than those of control rams at 7 and 60 weeks of age in Merino rams and at 23 and 31 weeks of age in crossbred rams. Plasma FSH concentrations at 21 and 26 weeks of age in the Merino rams immunized from 3 weeks of age were higher than those of control lambs, and these increases preceded a significant (P less than 0.05) increase in testicular diameter at 30 weeks of age (4.99 +/- 0.2 vs 4.37 +/- 0.2 cm). These results suggest that active immunization early in life with an inhibin-enriched fraction from bFF advances puberty in ewe lambs.(ABSTRACT TRUNCATED AT 400 WORDS)     

Weight, composition, mitosis, cell death and content of progesterone and DNA in the corpus luteum of pregnancy in the ewe

Changes in luteal weight from about Day 20 to near term, and in quantitative histology as assessed by ultrastructural morphometry and light microscopic counts of mitosis and cell death on Days 30, 60, 100 and 142, were studied in 168 pregnant ewes. Luteal weight (mean +/- s.d.) remained constant at 0.56 +/- 0.11 g until Day 120, and fell thereafter to reach 0.31 +/- 0.11 g after Day 140 (P less than 0.01). Up to Day 100, quantitative aspects of the composition of the luteal tissue showed no significant change, and values for volume density, cytoplasmic:nuclear ratio, cell number/mm3 and cell volume were comparable to values previously obtained for corpora lutea (CL) of the cycle. By Day 142 structural evidence of luteal regression was present, but regressive changes were much more marked in some CL than others. Mitosis was seen in a few cells (0.02-0.04%) on all of the days studied, but never in large luteal cells. Cell death was rarely seen up to Day 100, but had increased in incidence by Day 142 (P less than 0.01). Luteal progesterone content, 55.2 +/- 15.9 nmol/g on Day 30, was not significantly changed on Days 60, 100 or 142. It is concluded that (1) structural regression of the CL of pregnancy does not begin until much later than the time (about Day 50) when pregnancy ceases to depend on the CL; (2) structural luteal regression begins before parturition, but its time of onset and/or rate of progression vary widely between animals; and (3) large and small luteal cells remain as distinctive populations throughout pregnancy, and their numbers at all stages can be accounted for by survival of the cells which differentiate during the genesis of the CL.     

Crystallization and preliminary X-ray analysis of nonglycosylated tissue inhibitor of metalloproteinases-1, N30QN78Q TIMP-1

A nonglycosylated (N₃₀QN₇₈Q) form of the human tissue inhibitor of metalloproteinases, TIMP-1, has been prepared and crystallized in a form suitable for X-ray diffraction analysis. Small single crystals have been grown using sodium tartrate as a precipitant. The crystals are in space group P2₁, with cell dimensions a = 35.28, b = 53.95, c = 48.56, and β = 96.0°. There is a single molecule of TIMP-1 in the asymmetric unit. The crystals diffract to at least 2.3 Å resolution. Complete data have been collected to 2.9 Å and a search for heavymetal derivatives is in progress. © 1993 Wiley-Liss, Inc.     

The use of fluorescein-dipalmitoylphosphatidylethanolamine for measuring pH-changes in the internal compartment of phospholipid vesicles

The synthesis and characterisation of fluorescein-phosphatidylethanolamine (FPE) is described. The effects of dielectric constant, ionic strength and ambient pH upon the optical absorbance properties of FPE are presented. It is shown that under appropriate conditions, FPE rapidly and quantitatively reports the pH of the aqueous bulk phases when incorporated into phospholipid vesicles. It is also shown that, when the external medium is highly buffered, FPE is capable of specificity reporting only the pH of the intravesicular compartment. The application of FPE for studies of intravesicular pH changes of reconstituted membranous protein systems is discussed.     

Ultrastructure of the theca interna of ovarian follicles in sheep

Summary The theca interna of non-atretic ovarian follicles from 2.0 mm in diameter up to the stage shortly following ovulation was studied by light and electron microscopy.In follicles <3.0mm in diameter, the theca interna consisted of about 8–12 layers of flattened cells, together with many capillaries and small bundles of collagen. Two main forms of cellular differentiation were seen. These were towards either fibroblast-like cells or presumed steroidogenic cells whose cytoplasm contained large amounts of predominantly smooth tubular endoplasmic reticulum, to which some ribosomes were attached. The majority of cells were of relatively undifferentiated or intermediate structure.In larger follicles up to the early stages of oestrus the theca interna cells became larger and less flattened, and cells rich in tubular endoplasmic reticulum became proportionately more numerous. By 18 h after the onset of oestrus the theca interna was oedematous, and many cells possessed pseudopodia. Many cells also contained numerous lipid droplets, but there were no signs of thecal cell degeneration or death. Shortly after ovulation the basal lamina of the membrana granulosa was incomplete, and it became more difficult to distinguish between theca and granulosa layers. Structural heterogeneity, with two major cell types and cells of intermediate structure, was present at all stages.It was concluded that: (1) the theca interna of 2.0–2.9 mm follicles contained many cells whose structure was compatible with a steroidogenic capacity; (2) changes in the differentiated thecal cells up to the early stages of oestrus were quantitative rather than qualitative, and suggestive of an increased steroidogenic capacity; (3) the accumulation of lipid in many cells of the theca interna by 18 h after the onset of oestrus probably reflected a reduction in steroidogenic activity; and (4) there was no evidence of any structural specialization to facilitate the transport of steroids from the theca interna to the membrana granulosa.