Down Regulation

Last Updated: April 3, 2017

Definition - What does Down Regulation mean?

Down regulation is a process of reducing the sensitivity of a cell to specific hormone or chemical. This is achieved reducing the number of receptors on the surface of the cell. Receptors are how the cell can process and receive signals that come from outside of the cell. When an external substance binds to a receptor, it fits like a key in a lock and the receptor becomes full. Once this binding occurs, the substance can then provide directions to the cell on what is should do (release a substance etc.). The more cell receptors available, the greater the response to the external substance.

With down regulation, the cell's receptors are overexposed to an external substance (often a hormone) and this exposure causes the body to decrease the number of receptors on the cell's surface, which in turn has the effect of reducing the cell's sensitivity. During fertility treatments, there are a number of medications that are used to down-regulate various aspects of the female reproductive system.

FertilitySmarts explains Down Regulation

During an in vitro fertilization (IVF) cycle, gonadotropin-releasing hormone (GnRH) agonists such as Lupron, Synarel, Suprecur, or Buserelin are used in order to prevent premature ovulation. Preventing premature ovulation is important in controlled ovarian stimulation (COS) protocols, especially in older women who have a smaller ovarian reserve. It ensures that ovulation occurs at the right time, with fully developed follicles, in preparation for an egg retrieval procedure.

This is done through a process of down-regulating both follicle-stimulating hormone (FSH) and luteinizing hormones (LH). FSH is essential for follicle development and LH is essential for ovulation as well as androgen (male hormone) production.

At first, GnRH agonists mimic gonadotropin-releasing hormone (GnRH), which causes FHS and LH release at high levels. However, as they continue to stimulate hormone release, the body is overwhelmed and reduces the number of receptors on the cellular surface of the pituitary (master hormone gland) and the ovaries. The result is a reduced response to FSH and LH, which results in preventing ovulation.

Gonadotropin-releasing hormone (GnRH) agonists are given most commonly as a "long-protocol" to ensure the down-regulation of FSH and LH. Usually, they are started 7 days prior to the next expected period. They are dose-adjusted and given along with an FSH drug within 2-7 days to ensure proper egg development. Ovulation-stimulating drugs are introduced later in the cycle for controlled ovarian stimulation. It is important to know that there are many different protocols used for GnRH agonists that depend on the patient's response and history as well as the physician's practice.

GnRH agonists are used to down-regulate LH in women with polycystic ovary syndrome (PCOS). Keeping LH low has also shown to improve fertility outcomes as women with PCOS often have higher androgen levels which can cause abnormal egg and embryo development.

GnRH agonists can cause a menopausal state called pseudomenopause by reducing the production of FSH and LH. This is why common side effects include hot flashes, sweating and vaginal dryness. Other side effects include headache, dizziness, gastrointestinal upset, acne, and vaginal bleeding.

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