Isam Suliman

Prolactin binding sites in rat brain and liver: effects of long-term ovariectomy and ovarian steroids

The effects of long-term ovariectomy on the levels of brain and liver lactogenic binding sites as well as plasma and liver prolactin (PRL) have been investigated in sham-operated and ovariectomized rats receiving either 17 beta estradiol (OVX-E), progesterone (OVX-P), or vehicle (OVX-V). The levels of lactogenic binding sites in the parietal and piriform cortices, amygdala, thalamus, hypothalamus, as well as in the liver were significantly decreased after long-term ovariectomy. Moreover, the levels of plasma and liver PRL were also significantly decreased. Exogenous estradiol and progesterone replacement restored the levels of lactogenic binding sites in the parietal cortex and hypothalamus as well as in the liver. However, plasma and liver PRL levels were significantly increased by estradiol but only restored by progesterone. These results suggest that ovarian steroids influence the levels of lactogenic binding sites and prolactin.

Estrogen and progesterone treatment: effects on muscarinic M4 receptor subtype in the rat brain

We investigated the effect of ovariectomy (OVX) and hormonal treatment for 10 weeks by estradiol and progesterone on muscarinic M(4) receptor subtype in different brain areas of female rats. Moreover, motor activity of OVX and hormone-treated rats was measured by automated open field exploration boxes. Receptor quantification in the hippocampus, frontal cortex, parietal cortex, amygdala and hypothalamus was done by receptor autoradiography using a selective ligand for muscarinic M(4) receptors. Ovariectomy up-regulated M(4) receptors in the dentate gyrus, CA1, CA3, frontal cortex and hypothalamus whereas the estrogen treatment restored M(4) binding to that of the sham group. Progesterone treatment had no effect on the ovariectomy-induced up-regulation of M(4) receptors. Ovariectomy significantly decreased the exploratory activity of the rats compared to the sham group. Estrogen treatment restored the exploratory behavior of the ovariectomized rats to that of the sham group whereas the progesterone-treated rats were less alert to the surrounding when compared to the sham and estrogen supplemented rats. The effect of estrogen on the hippocampal muscarinic M(4) receptor subtype is a novel finding and may have functional significance for cholinergic receptors especially in relation to postmenopausal memory problems and neurodegenerative disease like Alzheimers disease.

Prolactin, growth hormone, and IGF-1 in ankles and plasma of adjuvant arthritic rats.

In this study we have investigated the levels of prolactin, growth hormone, and insulin-like growth factor-1 in plasma and in tissue extracts of ankle joints of rats with acute or chronic adjuvant arthritis using enzyme immunoassay (EIA) and radioimmunoassay (RIA). We found a stable content of prolactin in plasma of the different groups but a significantly increased concentration of growth hormone was observed in the plasma of the group with chronic arthritis. Moreover, an increased concentration of insulin-like growth factor-1 was noted in the plasma of the acute group. This evidently had returned to normal levels in the chronic group. In contrast, decreased concentrations of prolactin, growth hormone, and insulin-like growth factor-1 were found in tissue extracts of ankle joints of the group with chronic arthritis. The changes in the levels of these hormones in adjuvant arthritis might suggest that they play a role in the pathogenesis of the disease. Understanding the mechanism(s) of hormonal participation in adjuvant arthritis may open new treatment strategies for rheumatoid arthritis and other inflammatory disorders.

Intracerebroventricular administration of somatostatin prevents and attenuates adjuvant arthritis

The effects of somatostatin on the development of adjuvant arthritis induced by Mycobacterium butyricum were studied. Somatostatin was injected into the lateral cerebral ventricle every day for 14 days beginning on the first day of mycobacteria inoculation in the preventive group. In the treatment group, somatostatin was injected from day 17 until day 30 post-mycobacteria inoculation. Arthritis was evaluated by measuring ankle joint circumference and diameter as well as microscopic examination of ankle joint sections. Somatostatin profoundly inhibited the development of adjuvant arthritis and an anti-inflammatory action was observed in the treatment group. These results suggest that somatostatin has a central action that can prevent or attenuate symptoms associated with arthritis.

Effects of short- and long-term rat hind limb immobilization on spinal cord insulin-like growth factor-I and its receptor.

In this study we investigated changes in the spinal cord insulin-like growth factor-I peptide (IGF-I) and its receptors (IGF-IR) after hind limb immobilization for 5 days, 2, 4, and 8 weeks. Moreover, effects on IGF-I and nicotinic cholinergic receptors (nAChRs) in two types of skeletal muscle were also investigated. IGF-I levels were measured by radioimmunoassay (RIA) whereas IGF-IR and nAChRs were measured by quantitative receptor autoradiography. Spinal cord IGF-I levels decreased significantly after 5 days, 2 and 4 weeks of immobilization, whereas IGF-IR increased significantly after 4 and 8 weeks compared to controls. In skeletal muscles, nAChRs increased significantly after 5 days and 2 weeks in the soleus (SOL) and tibialis anterior (TIB) muscles, respectively, and continued up to 8 weeks in both muscles. IGF-I concentration decrease significantly after 4 and 8 weeks in the SOL and TIB muscles, respectively. Despite the normal levels of IGF-I in both muscles at the early time points (5 days and 2 weeks), low levels of IGF-I were observed concurrently in the spinal cord ipsilateral to the immobilized limb. Our findings suggest that the early decrease in the IGF-I level and the late upregulation in the IGF-IR in the spinal cord might represent a nervous system response to disuse.

Intracerebroventricular met-enkephalin administration modulates adjuvant arthritis.

The purpose of this study was to investigate the anti-inflammatory properties of intracerebroventricular met-enkephalin (met-enk) administration in an animal model of arthritis. Adjuvant arthritis was induced in rats by intradermal inoculation of mycobacterium butyricum and the effects of intraventricular met-enk+thiorphan (enkephalinase inhibitor) were studied. Treatment was initiated either simultaneously with the bacterial inoculation (preventive group) or on post-inoculation day 17 after the appearance of inflammation (treatment group). The degree of inflammation was evaluated by measuring the diameter and the circumference of the ankle joint immediately before the sacrifice (day 31) and by histologic examination of ankle joint sections. The results of this study revealed that combined intraventricular injections of met-enk+thiorphan reduced the arthritic-like inflammation in the preventive group as well as in the treatment group. These findings suggest that centrally applied met-enk+thiorphan may suppress the development adjuvant arthritis as well as the symptoms of manifest arthritis. Thus central met-enk may be involved in both hypothalamic pituitary adrenal axis and immune forms of stress-induced modulation.

Effects of long-term ovariectomy and ovarian steroids on somatogenic binding sites in rat brain and liver ☆

The effects of long-term ovariectomy and replacement with ovarian steroids on the levels of brain and liver somatogenic binding sites as well as plasma and liver growth hormone (GH) were studied in sham-operated (Sham) and ovariectomized female rats receiving either, 17 beta-estradiol (OVX-E), progesterone (OVX-P), or vehicle (OVX). Long-term ovariectomy decreased the levels of somatogenic binding sites in the choroid plexus and liver as well as GH in plasma and liver. The levels of these sites in the choroid plexus were partially restored only by estradiol replacement. Moreover, exogenous estradiol but not progesterone restored the levels of plasma and liver GH as well as liver somatogenic binding sites. Our results suggest that estrogens regulate the levels of somatogenic binding sites in the liver and choroid plexus.

Ultrastructural analysis of the hippocampus of adult rats after long-term adrenalectomy.

Removal of adrenal steroids modulates various functions in the brain. However, adrenalectomy (ADX) induced cell death in the hippocampal formation of the adult rat is a recently described phenomenon. We undertook this ultrastructural study on long-term adrenalectomized (5 months) rats to investigate the mode of cell death in the hippocampus. Our results showed apoptotic changes in the hippocampus. In addition we have observed other types of degeneration in the hippocampal neurons. The novel finding in this study is that different morphological patterns of cell death were evident both in the dentate gyrus and in the pyramidal areas, which may reflect different stages of the same death process.

The effect of ovariectomy and ovarian steroid treatment on growth hormone and insulin‐like growth factor‐I levels in the rat femur

Growth hormone (GH) and insulin‐like growth factor‐I (IGF‐I) are known to play an important role in bone metabolism. The regulation of plasma levels of GH and IGF‐I by ovarian steroids is well known, however, their effect on local GH and IGF‐I is still unclear. In this study, we investigated the effect of ovariectomy and ovarian steroid treatment on the femur GH and IGF‐I levels as well as on bone density in the rat. Nine month‐old rats were ovariectomized (OVX) or sham‐operated (SHAM) and 9 weeks after the surgery they were treated with daily s.c. injections of either 17β‐estradiol (OVX + E), progesterone (OVX + P), or vehicle (OVX + V) for another 10 weeks. GH and IGF‐I levels in the femur extracts were measured by specific radioimmunoassay (RIA). Ovariectomy decreased GH and had no effect on IGF‐I levels. Estradiol treatment increased femur GH and IGF‐I levels compared to SHAM rats. Progesterone restored GH and increased IGF‐I levels. Ovariectomy decreased, estrogen restored and progesterone partially restored femur bone density. Our results demonstrate that ovariectomy and ovarian steroids modulate the levels of GH and IGF‐I in the bone of aged OVX rats. However, these effects appear to be limited to supraphysiological concentrations of estradiol and progesterone.

Changes in Tissue levels of Growth Hormone, insulin-like growth Factor-I, and Somatostatin in the Femurs of Hind-limb Immobilized Rats

Immobilization of an extremity causes skeletal muscle atrophy and a dramatic increase in bone resorption. Growth hormone (GH) is known to play an important role in bone remodeling mediated in part by local insulin-like growth factor-I (IGF-I). In this study, we investigated changes in the levels of GH and IGF-I peptide in bone extracts from the femur after hind-limb immobilization for 5 days, 2, 4, and 8 weeks. The levels of somatostatin, which interacts with GH, were also measured in the bone extracts. GH levels increased after 8 weeks of hind-limb immobilization whereas the IGF-I concentrations increased after 2 weeks, but returned to control levels at 4 weeks, and decreased after 8 weeks of immobilization. The somatostatin levels in the bone extracts increased only after 8 weeks of hind-limb immobilization. Our findings suggest that, after hind-limb immobilization, changes in the concentrations of GH, IGF-I, and somatostatin in bone may mediate bone resorption either directly or through interaction with other factors.