Early Prediction of Long-Term Response to Cabergoline in Patients with Macroprolactinomas

BACKGROUND: Cabergoline is typically effective for treating prolactinomas; however, some patients display cabergoline resistance, and the early characteristics of these patients remain unclear. We analyzed early indicators predicting long-term response to cabergoline. METHODS: We retrospectively reviewed the cases of 44 patients with macroprolactinomas who received cabergoline as first-line treatment; the patients were followed for a median of 16 months. The influence of various clinical parameters on outcomes was evaluated. RESULTS: Forty patients (90.9%) were treated medically and displayed tumor volume reduction (TVR) of 74.7%, a prolactin normalization (NP) rate of 81.8%, and a complete response (CR; TVR >50% with NP, without surgery) rate of 70.5%. Most patients (93.1%) with TVR > or =25% and NP at 3 months eventually achieved CR, whereas only 50% of patients with TVR > or =25% without NP and no patients with TVR 25% at 3 months without NP, particularly those with huge prolactinomas, because a delayed response may be achieved. As surgery can reduce the cabergoline dose necessary for successful disease control, it should be considered for cabergoline-resistant patients.

Successful Graft Recovery from Thrombotic Acute Kidney Injury in a Kidney Transplant Patient with Antiphospholipid Syndrome / 대한이식학회지

Antiphospholipid syndrome nephropathy (APSN) is well documented in the literature as the renal involvement of the antiphospholipid syndrome (APS). A review of literature also shows that among antiphospholipid antibodies, lupus anticoagulant (LA) positivity is recognized as the strongest risk factor for APSN. In addition, APSN is also known to be associated with a poor functional outcome in the first posttransplant year. Therefore, it is a general belief that renal transplantation may be life threatening in APS patients. Furthermore, the presence of LA at the time of transplantation is particularly associated with a high rate of allograft APSN and the consequent poor transplantation outcomes. Here, we report the case that thrombotic acute kidney injury due to APSN after kidney transplantation can be successfully treated if anticoagulation therapy is timely applied with a prompt diagnosis.

Neurochemical Identification of Hypothalamic Neurons Expressing c-Fos in response to Hypertonic Saline / 대한해부학회지

Previous studies have shown that hypertonic saline induces c-fos expression in the magnocellular neurons of rat hypothalamus. The present immunohistochemical double-labeling study was undertaken to determine the identification of magnocellular neurons expressing c-Fos in response to osmotic stimulus. Hypertonic saline induced c-Fos-like immunoreactivity (FLI) in various regions of hypothalamus in addition to supraoptic nucleus (SON) and paraventricular nucleus (PVN). FLI was detected in most of oxytocin neurons in the preoptic region and in the accessory nuclei located between the PVN and SON as well as in the SON and PVN. In particular, most of all oxytocin neurons in the accessory nuclei were labeled for c-Fos. There were also many FLI cells that did not show oxytocin and vasopressin immunore-acitivity in their cytoplasm. Relative frequencies of oxytocin and vasopressin neuronal responses showed that much more cells of oxytocin than vasopressin were induced to express c-fos in response to hypertonic saline. These data show that both oxytocin and vasopressin neurons are sensitive to osmotic stimulus and activated via expression of c-Fos by hypertonic saline.

Temporal Changes of c-fos, c-jun, and Heat Shock Protein 25 mRNA in Rat Uterus following Estradiol Treatment / 대한불임학회지

SUMMARY: Steroid hormone is known to cause the dynamic changes of mammalian uterus during reproductive cycle, which are modulated via hypothalamus-pituitary -gonad reproductive endocrine axis. Although there were so many studies about estrogenic regulation of uterine growth and differentiation. There is little information about the effect of estrogen on the expression of various transcription factors involved in gene expression. Thus the present study was designed to demonstrate E induced expression of c-fos, c-jun, hsp25 mRNA in rat uterus. Employing Northern blot analysis, we studied the temporal expressions of c-fos, c-jun, and hsp25 messenger RNAs (mNAs) elicited by a single 17beta-estradiol(E) treatment in the uteri of bilaterally ovariectomized adult rats. c-fos, c-jun, and hsp25 mRNA levels were increased and peaked at 3 h after E administration, and then c-fos and c-jun mRNA levels were rapidly decreased to basal control level while, increased hsp25 mRNA levels were sustained till 12 h post E treatment. To test the estrogenic effect on the increase of c-fos, c-jun, and hsp25 mRNA levels, we also examined the effects of antiestrogen (tamoxifen). Pretreatment with tamoxifen effectively blocked the E-induced increase of c-fos, c-jun, and hsp25 mRNA levels at 3 h post E treatment. Present results suggest that transient increase of c-fos and c-jun protooncogene mRNA at the early time and simultaneous expression of hsp25 mRNA contribute to the response of uterine tissues to E in adult female rats.

Expression of Luteinizing Hormone (LH) Gene in Rat Uterus and Epididymis / 대한불임학회지

Recent studies clearly demonstrated that the novel expression of LH gene in the rat testis, and suggested the local action of the LH-like molecule. The present study was performed to analyze the expression of the LH genes in the rat accessory reproductive organs. Expression of LH subunit genes in the rat uterus and epididymis was demonstrated by reverse transcription-polymerase chain reaction (RT-PCR) and specific LH radioimmunoassay (RIA). The LHbeta transcripts in these organs contained the published cDNA structure, the pituitary type exons 1-3, which encoded the entire LHbeta/ polypeptide. Presence of the transcripts for the alpha-subunit in the rat reproductive tissues were also confirmed by RT-PCR. In the LH RIA, significant levels of LH were detected in crude extracts from the rat ovary, uterus and epididymis. The competition cuties with increasing amount of tissue extracts were parallel with those of standard peptide, indicating that the immunoreactive LH-like materials in these tissues are similar to authentic pituitary LH molecule. In rat epididymis, the highest amount of immunoreactive LH was detected in corpus area. Our findings demonstrated that the genes for LH subunits are expressed in the rat accessory reproductive organs, and suggested that these extrapituitary LH may act as a local regulator with auto and/or paracrine manner.

Studies on the Activation of Neurons involved in Osmoregulation in Developing and Aging Rat / 대한해부학회지

Previous studies by others have shown that administration of hypertonic saline (HS) induces c-fos expression in rat brain and old fibroblast cells are defective in transcription of c-fos in response to serum. The present immunohisto-chemical studies were undertaken to determine 1) the time that c-fos is expressed during the postnatal development of rat brain and 2) if there is aging-related change of c-fos expression in the osmoresponsive neurons after osmotic stimulus. Fos-like immunoreactivity (FLI) in response to HS treatment began to be detected dramatically at postnatal day (P) 14 in hypothalamic paraventricular nucleus (PVN), supraoptic nucleus (SON), and organum vasculosum lamina terminalis (OVLT). Intensity of FLI and number of Fos immunoreactive cells induced by HS were substantially reduced as rats age. Our data demonstrate for the first time that c-fos induction is decreased in aging-dependent manner and the time of c-fos induction during postnatal development is coincided with the status of differentiation in rat brain. We will interpret these findings in relation to synaptogenesis, and maturation or disability of signal transduction pathways in osmoresponsive neurons in rat brain.

Effect of Steroid Hormones on the Expression of c-Fos, CREB, ATF, and HSP70 in Rat Uterus / 대한불임학회지

Steroid hormone is known to cause the dynamic changes of mammalian uterus during reproductive cycle. However there is little information about the effect of estrogen (E) and progesterone (P) on the expression of various transcription factors involved in gene expression. Thus the present study was designed to demonstrate E and/or P-induced expression of c-Fos, CREB, ATF and HSP70 in rat uterus. Rats, ovariectomized (OVX) for two weeks, were divided into 6 experimental groups, 1) OVX, 2) OVX+V, 3) OVX+E, 4) OVX+P, 5) OVX+E+V, 6) OVX+E+P, and western blotting assay for nuclear extract and immunohistochemical staining were carried out for each experimental group. Treatment of E (10microgram) showed to increase the expression of c-Fos, CREB, ATF, and HSP70, and maximal expression was occured at 3~6 hr after E administration. P (1mg) also increased, but much less than E, the expression of c-Fos, ATF, and HSP70. However, P did not reveal any effect on the expression CREB. P treatment 4 hr after E injection decreased c-Fos, CREB, and ATF expression, but did not show any change in the E-induced HSP70 expression. In immunohistochemical study c-Fos-, CREB-, and ATF-immunoreactivities were conficed to the cells of luminal epithelium of uterine endometrium. These results suggest that proliferation and differentiation of rat uterus during reproductive cycle may mediated via expression of transcription factors, such as c-Fos, CREB, ATF, and HSP70.