Endocrine feedback

A loss of primary oocytes will irreversibly affect a woman s fecundity, but this is difficult to measure directly. Reproductive dysfunction can be studied by the evaluation of irregularities of menstrual cycles and onset of menarche and menopause. However, menstrual cyclicity and onset of menopause and menarche are affected by many parameters, such as age, genetics, nutritional status, stress, exercise, certain drugs and the use of contraceptives that alter endocrine feedback. The length of the menstrual cycle, particularly the follicular phase (before ovulation), can vary between individuals and may make it difficult to measure significant effects in groups of women (Burch et al., 1967 Treloar et al., 1967). 

Figure 33.2. Endocrine feedback loops of the mammalian hypothalamic-pituitary-gonadal (HPG) axis. (Adapted from La Barbera A. R. Differentiation and function of the female reproductive system. In Boekelheide, K., Chapin, R. E., Hoyer, P. B., and Harris, C. (Eds.). Comprehensive Toxicology, Vol. 10, Reproductive and Endocrine Toxicology, Elsevier, New York, 1997, pp. 255-272 and Creasy, D. M., and Foster, P. M. D. Male reproductive system. In Haschek, W. M., Rousseaux, C. G. and Wallig, M. A. (Eds.). Handbook of Toxicologic Pathology, 2nd ed., Academic Press, San Diego, 2002,pp. 785-846. E2, estradiol T, testosterone, DHT, dihydrotestosterone, FSH, follicle stimulating hormone LH, luteinizing hormone.

Both the ANS (neural) and endocrine feedback loops are invoked when patients are treated with antihypertensive drugs. Such compensatory mechanisms may result in tachycardia and both salt and water retention. 

Reports of the effects of Li+ upon the thyroid gland and its associated hormones are the most abundant of those concerned with the endocrine system. Li+ inhibits thyroid hormone release, leading to reduced levels of circulating hormone, in both psychiatric patients and healthy controls [178]. In consequence of this, a negative feedback mechanism increases the production of pituitary TSH. Li+ also causes an increase in hypothalamic thyroid-releasing hormone (TRH), probably by inhibiting its re-... 

Wersinger SR, Haisenleder DJ, Lubahn DB, Rissman EF (1999) Steroid feedback on gonadotropin release and pituitary gonadotropin subunit mRNA in mice lacking a functional estrogen receptor a. Endocrine 11 137-143... 

GHRF and GHRIF are peptides secreted by hypothalamic neurons termed neuroendocrine transducers (the name is apt, as these interface between the nervous and endocrine systems). The factors that regulate their secretion are poorly understood but probably involve both nerve impulses originating from within the brain and feedback mechanisms, possibly involving pituitary hormones. 

The nervous system has several properties in common with the endocrine system, which is the other major system for control of body function. These include high-level integration in the brain, the ability to influence processes in distant regions of the body, and extensive use of negative feedback. Both systems use chemicals for the transmission of information. In the nervous system, chemical transmission occurs between nerve cells and between nerve cells and their effector cells. Chemical transmission takes place through the release of small amounts of transmitter substances from the nerve terminals into the synaptic cleft. The transmitter crosses the cleft by diffusion and activates or inhibits the postsynaptic cell by binding to a specialized receptor molecule. In a few cases, retrograde transmission may occur from the postsynaptic cell to the presynaptic neuron terminal. 

FIGURE 23-11 Cascade of hormone release following central nervous system input to the hypothalamus. In each endocrine tissue along the pathway, a stimulus from the level above is received, amplified, and transduced into the release of the next hormone in the cascade. The cascade is sensitive to regulation at several levels through feedback inhibition by the ultimate hormone. The product therefore regulates its own production, as in feedback inhibition of biosynthetic pathways within a single cell. 

Kalra SP, Kalra PS. Neuropeptide Y. A physiological orexigen modulated by the feedback action of ghrelin and leptin. Endocrine. 2003 22 49-56. 

There are also a few examples of positive feedback mechanisms in the endocrine system.25 43 In a positive feedback loop, rising concentrations of one hormone cause an increase in other hormones, which, in turn, facilitates increased production of the first hormone. The primary example of this type of feedback occurs in the female reproductive system, where low levels of estrogen production increase the release of pituitary hormones (LH, FSH).10 43 Increased LH and FSH then facilitate further estrogen production, which further increases pituitary hormone secretion, and so on (see Chapter 30). Positive feedback mechanisms are relatively rare, however, compared with negative feedback controls in the endocrine system. 

The presence of feedback systems in endocrine function is important from a pharmacologic perspective. Drugs can be administered that act through the intrinsic feedback loops to control endogenous hormone production. A primary example is the use of oral contraceptives, when exogenous estrogen and proges-... 

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