SHBG synthesis  

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oswaldosalcedo
(@oswaldosalcedo)
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11/09/2018 2:51 am  

The relationship between serum levels of insulin and sex hormone-binding globulin in men: the effect of weight loss.

Strain G, Zumoff B, Rosner W, Pi-Sunyer X.

Division of Endocrinology and Metabolism, Mount Sinai Medical Center, New York, New York 10029.

It is known that there is an inverse relationship between the serum levels of insulin and sex hormone-binding globulin (SHBG) in women, but the relationship in men has not been reported. It is not known whether changes in the one cause changes in the other, or whether they change in opposite directions in response to some third factor. Because obesity raises insulin levels and lowers SHBG levels in both sexes, we proposed to study the cause-effect question by determining whether the relationship between changes in SHBG and insulin levels during active weight loss. We studied 70 healthy weight-stable men with body mass index (BMI) from 20.7-94 (normal, 22.5 +/- 2.5) and restudied 17 of them during diet-induced weight loss. Fasting serum insulin levels in the weight-stable men showed a positive linear correlation with BMI, increasing 1 microU/mL per unit increase in BMI (P < 0.0001). SHBG levels in the weight-stable men showed a negative linear correlation with BMI, decreasing 0.2 nmol/L per unit increase in BMI (P < 0.0002). In the weight-stable men, there was an inverse hyperbolic correlation between SHBG and insulin levels; SHBG (nmol/L) = 13.1 + [30.1 divided by insulin (microU/mL)] (P < 0.002). During weight loss, insulin levels decreased at an average rate of 6.1 microU/mL per unit decrease in BMI, a much higher slope than the positive slope vs. BMI in weight stable men. During weight loss, SHBG levels increased at an average slope of 0.43 nmol/L per unit decrease in BMI, much higher than the negative slope of 0.2 nmol/L per unit increase in BMI in weight-stable men. Values for the SHBG vs. insulin coordinates in the weight-losing subjects did not differ significantly from those expected from the SHBG vs. insulin equation in weight-stable subjects. The stability of the SHBG-insulin relationship during weight loss despite the profoundly altered relationship of each separate component to BMI strongly suggests a close metabolic link between SHBG and insulin. As SHBG is not known to alter the production or metabolism of insulin, whereas insulin has been shown in vitro to decrease the synthesis of SHBG, it seems a reasonable conclusion that the predictable inverse relationship between serum insulin and SHBG indicates that insulin controls SHBG synthesis in vivo.


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Big Cat
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11/09/2018 3:48 am  

Nice find.

Goes again to show the correlation between SHBG and total as well as free Testosterone levels, since obese and diabetic individuals generally have lower total and free testosterone levels.

Good things come to those who weight.

The Big Cat is a researcher and theoreticist. His advice must never be taken in the stead of proper advice from a medical professional, it is entirely intended for research purposes.


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pSimonkey
(@psimonkey)
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11/09/2018 4:32 am  

so would that suggest that one would need to diet-up and diet-down to potentiate both insulin and then SHBG, naturally, that is?


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Big Cat
(@big-cat)
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11/09/2018 5:04 am  

I wouldn't worry too much about manipulating insulin. If you manipulate it to a point where you get high levels and low sensitivity, you are going about it all wrong.

Only siutuation that warrants that is if you see a need to use exo insulin at some point, and then it should be obvious that you should continue using steroids for some time after cessation of insulin and prepare your PCT very well.

If you go about it all naturally, your insulin and sensitivity shouldn't get to a point where it lowers your total and free test.

Good things come to those who weight.

The Big Cat is a researcher and theoreticist. His advice must never be taken in the stead of proper advice from a medical professional, it is entirely intended for research purposes.


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liftsiron
(@liftsiron)
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11/09/2018 6:01 am  

The study didn't refer to weight training during weight loss nor did it state if there was a moderate or severe restriction of calories.

liftsiron is a fictional character and should be taken as such.


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oswaldosalcedo
(@oswaldosalcedo)
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Posts: 39
11/09/2018 6:33 am  
Posted by: liftsiron
The study didn't refer to weight training during weight loss nor did it state if there was a moderate or severe restriction of calories.

We studied 70 healthy nondieting weight-stable men with a body
mass index [BMI = weight (kg) - height (m�)] ranging from 20.7-94
(upper limit of normal, -25). Subjects were excluded if there was a
history of any major medical disorder, if they were taking any medication, or if there was clinical or laboratory evidence of renal, hematological, hepatic, or thyroidal dysfunction. Weight was measured to the nearest 0.1 kg while the subject was wearing light clothing without shoes; height was measured to the nearest 0.5 cm under the same conditions. Subjects were instructed to eat their usual diets and to make no effort to lose weight. After 1 week, blood was drawn from each subject after a 12-h fast. Serum SHBG concentration was measured in 64 of the subjects and serum insulin concentration was measured in 30; both concentrations were measured in 24 subjects.Insulin (14) and
SHBG (15) were quantitated by RIA. Correlations were made between SHBG and BMI, insulin and BMI, and SHBG and insulin. Regression equations for hyperbolic, logarithmic, power-function, and linear correlations were calculated by computer, using a curve-fitting program, and the equation showing the highest correlation coefficient was used for analysis. Seventeen of the obese subjects (initial BMI, 37-94) were then given low calorie, low fat, high fiber, weight loss diets as outpatients. After 6 weeks to 39 months, when they had lost 1.7-129 kg (1.2-47.4 BMI units) and were still on their diets, the fasting serum insulin concentration was redetermined in all of them, and the fasting serum SHBG concentration was redetermined in 16....................................SHBG binds to target tissues (16, 17) and inhibits androgenic hormone uptake (18), but has no known direct effect on the biosynthesis of insulin. Conceivably, it might have an indirect effect via its influence on serum free testosterone and estradiol levels; in both men and women, the percentage of circulating testosterone and estradiol that is free, and therefore biologically active, rises when SHBG levels fall and vice versa. In obese women, in whom SHBG levels fall (1, 9), the absolute serum concentrations of both free testosterone and free estradiol rise (1, 9); in obese men, in whom SHBG levels also fall (1 l), the absolute concentrations of free estradiol rise (9, 19), but the absolute concentrations of free testosterone fall (9). Administration of testosterone to men does not significantly affect their serum insulin levels (20); the effect on insulin levels in women is unknown. The fact that in obesity decreased SHBG levels are associated with elevated free testosterone levels in women but decreased free testosterone levels in men (9), whereas both sexes show increased insulin levels, effectively eliminates any possible role for altered free testosterone as a mediator by which SHBG might control insulin levels. Administration of estrogens to women lowers their serum insulin levels (21); the effect on insulin levels in men is unknown. Higher SHBG levels would lower serum free estradiol levels and, therefore, might be expected to raise insulin levels if the relationship seen in women holds in men, i.e. the relationship between SHBG and insulin levels would be the opposite of what is
observed. In contrast, insulin has been specifically demonstrated in vitro to inhibit the synthesis of SHBG (8), so it seems most
reasonable to conclude that the constant relationship of
serum SHBG and insulin levels reflects a dominant role of
insulin in controlling the production of SHBG. Thus, our in
vim data support the conclusions derived from previous in
vitro studies.

1. Evans DJ, Hoffman RG, Kalkhoff RK, et al. Relationship of
androgenic activity to body fat topography, fat cell morphology,
and metabolic aberrations in premenopausal women. J Clin Endocrinol Metab. 57:304-310.

8. Plymate SR, Matij LA, Jones RE, et al. Inhibition of sexhormone-binding globulin production in the human hepatoma (Hep 62) cell line by insulin and prolactin. J Clin Endocrinol Metab.67:460-464.

9. Zumoff B. Hormonal abnomalities in obesity. Acta Med Scand.723(Suppl)153-160.
723(Suppl):153-160.

19. Schneider G, Kirschner MA, Berkowitz R, et al. Increased
estrogen production in obese men. J Clin Endocrinol Metab. 48:633-638.

20. Marin P, Holmang S, Jonssen L, et al. The effects of testosterone treatment in body competition and metabolism in middleaged obese men. Int J Obesity. 16:991-997.

21. Barrett-Connor E, Laaksen M. Ischemic heart disease risk in postmenopausal women. Effects of estrogen use on glucose and insulin levels. Arteriosclerosis. 10:531-534.


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